Phytochemical, Pharmacological, Toxicological, and Nanotechnology Based Materialistic Approach of Fagonia Cretica Linn.

INTRODUCTION:

The term "naturally derived substances" is used in Ayurveda to describe everything that comes from a plant or an animal. The literature on Ayurveda extensively mentions the usage of Dhanvayasa and its component formulations for the treatment of Pitta-vitiated situations. Because plants contain a myriad of new components with varying therapeutic effects, botanical treatments have been used for human disease management for ages[1]. The 240 species belonging to 25 genera make up the Zygophyllaceae family, which is found only in arid tropical, subtropical, and warm temperate regions. Pharmacists are very interested in all plants belonging to this family, but especially those of the genus Fagonia, because early pharmacological research has shown that these plants have effective therapeutic potential for the treatment of a wide range of health problems[2]. The aqueous extract of the aerial portions of Fagonia Cretica Linn is a well-known medicine that has the potential to be very effective for early-stage cancer treatment. It has powerful curative powers against a wide range of neurological, inflammatory, haematological, and hepatic disorders. For example, Fagonia Cretica Linn and related species are thought to have analgesic, antidote, antidysenterica, antihepatotoxic, antipyretic, diuretic, and anti-asthmatic properties. Many different chemical components, such as flavonoids, fatty acids, alkaloids, proteins, and more, have been isolated from Fagonia species through phytochemical research[3].

Many different active phytochemical components were thought to be responsible for the plant's medical effects. Despite the plant's numerous decades of phytochemical research, the chemical structures of its constituents have only been determined in the past fifteen years. Two main classes of phytochemical substances, flavonol glycosides, and terpenoid glycosides, were the primary targets of the investigation into the whole plants of different Fagonia species[4]. The evolutionary relationships of several flavonol glycosides were studied after their isolation from several species of Egyptian Fagonia. Additionally, several saponins or triterpenoid glycosides were isolated and studied. The aqueous extract of air-dried Fagonia Cretica Linn plants yielded water-soluble proteins, whereas the hexane extract yielded docosyldocosanoate and other components. Other Fagonia species' haegagenin, hederagenin, ursolic acid, and pinitol were also isolated and studied. There has been prior investigation into the potential antimicrobial effects of its flavonoid components. In traditional medicine, this herb has several different uses. Several national formularies have granted patents to their formulations[5].

Many gastrointestinal and circulatory disorders have found relief with this plant. The ethnomedicinal and pharmacological uses of this plant have been detailed in numerous researches. The application of nanotechnology to enhance the therapeutic benefits of Fagonia Cretica Linn extracts is highly encouraging. Utilising nanoscale structures and materials can improve the bioavailability, targeted distribution, and efficacy of plant phytochemicals. One way is to use nanoparticles that include extracts from Fagonia Cretica. Nanoparticles can prolong the shelf life of phytochemicals, increase their solubility, and facilitate their absorption. Furthermore, this encapsulation can be used to provide regulated release, which can decrease dosage frequency while prolonging therapeutic effects. Surface functionalization of nanoparticles also allows for targeted delivery to certain cells or tissues. By affixing ligands or antibodies to the surface of nanoparticles, they can be directed towards diseased cells, such as cancer cells, increasing therapeutic efficiency while minimising off-target consequences[6].This review article is based on the extensive literature study to report the phytochemical composition and medicinal potential of F. cretica L.

Characteristics of Fagonia Cretica Linn

The "Dhamasa" or "Dhamaas," a little perennial shrub known as Fagonia Cretica Linn, belongs to the family Zygophyllaceae. Its native range encompasses the arid and semiarid regions of India, Pakistan, Afghanistan, and Iran. This plant does best in sandy or rocky soils and thrives in hot, dry climates. With its numerous branches and small woody stems, Fagonia Cretica gives the impression of being a dense shrub. The small, opposite leaves can be either linear or lanceolate in shape and can have a greenish-gray colour. Whenever it rains, the plant responds by sending out clusters of small, single flowers, each with five petals that have a pale pink or white tint. The unique medicinal properties of Fagonia Cretica make it stand out among plants. Traditional herbal medicine systems, particularly in South Asia, have long made use of it due to its therapeutic value[7]. All parts of the plant, including the stems, flowers, and leaves, are used to extract its medicinal properties. Sweet, bitter, sharp, or sour flavours can develop at different points in the plant's life cycle and in response to different parts of the plant. The blossoms are a rich purple colour and there are a lot of little fruits near the thorns. Discoveries include additional components, including water-soluble proteins extracted from an aqueous extract of air-dried fagonia cretica plants and docosyldocosanoate derived from hexane extract. The dietary antimicrobial activity of nahagenin consisting of hederagnin, ursolic acid, and its flavonoid, has been investigated in earlier studies[8].

Habitat and geographical distribution

Fagonia cretica Linn, is a common plant in dry and semi-arid climates across Asia and the Middle East. Dry, rocky places, sandy soils, and desert plains are typical places it lives. The geographical distribution of Fagonia cretica includes several countries: Afghanistan, Pakistan, Iran, Saudi Arabia, Iraq, Jordan, and Syria, among others. Its native Indian habitats include the southern states of India, as well as the states of Rajasthan, Gujarat, and Maharashtra. Its distribution in Pakistan is similar, spanning the semi-arid and dry provinces of Balochistan, Khyber Pakhtunkhwa, Sindh, and Punjab. Due to its adaptations, Fagonia cretica can flourish in the dry, nutrient-poor soils typical of semi-arid and arid areas. Its widespread distribution is indicative of its habitat choice; in certain areas, it is an important part of the ecosystem and has great medicinal value in traditional medicine[9].

Medicinal outcomes of Fagonia Cretica Linn

A disease-free and healthy existence can be achieved with the help of medicinal plants, which are a gift from nature. A traditional remedy, fagaonia cretica has anti-septic, blood-purifying, and anti-bilious effects. Stomatitis and other oral disorders are treated internally with a decoction and gargled with it; boils, ulcers, and scrofulous glands are treated topically with a paste. People in the Indo-Pak subcontinent utilise this plant as a remedy for a wide variety of ailments, including typhoid, scabies, fever, asthma, urinary tract infections, bronchitis, tumours,liver problems, piles, and digestive disorders[10]. Included among its many ayurvedic compositions are chitrakadivati, duralabhadikwath, and Hirasawa. Externally, as a paste for tumours and for edema of the neck, the twigs of the plant are used as a snakebite cure. Rough phytochemical extracts and isolated compounds from fagonia cretica have been found to possess neuroprotective, anti-inflammatory, anti-tumor, and anti-hemorrhage activities. In addition to their anti-diabetic effects, fagonia cretica methanolic extracts have demonstrated promising antimicrobial, free radical scavenging, and reactive oxygen and nitrogen species activities[11].

Phytochemistry and chemical constituents of Fagonia Cretica Linn

Several compounds were extracted from the plant, including diosgenin, kryptogenin, lanosterol, harmine, fagogenin, and oleanolic acid. The hydrolysis of a glycoside yields chinovic acid, which is referred to as chinovin, or Harman. There were more compounds derived from the plant, including betulin, campesterol, stigmasterol, and triacontanol. Terpenoids of the oleanane group, saponins I and II, alkaloids (harmine), amino acids (alanine, glycine, leucine, arginine, isoleucine, lysine, phenylalamine, proline, tyrosine, and valine), and phenolic acid are present as well[4]. In addition to tannins, the leaves include orientin, vitaxin, bergapten, and saponarin. Important components of leaf essential oil include methyl chavicol, t-anethol, thymol, and p-cymen-z-ol. Alpha- and beta-pinene, sabinene, myrcene, beta-phellandrene, and p-cymene are among the others (Figure.1)[12].

Figure1. Chemical structure of compounds isolated from Fagonia Cretica Linn

Toxicological data of Fagonia Cretica Linn

Despite a lack of extensive toxicological data, research on Fagonia cretica has identified bioactive components including triterpenes, alkaloids, saponins, and flavonoids, all of which contribute to the plant's medical benefits. Nevertheless, there might be hazards to using it, as there are many natural medicines. Consuming too much Fagonia cretica may cause gastrointestinal problems, allergic responses, or liver damage, according to some research. Be aware that the effects of herbal supplements may differ from person to person and that they may interact negatively with other drugs or current health issues. Additional research is necessary to have a complete understanding of the safety profile and any harmful consequences of Fagonia cretica in people, despite its encouraging therapeutic promise in preclinical investigations for diseases such as inflammation, diabetes, and cancer. Before using Fagonia cretica, especially at high doses or for an extended period, it is recommended to visit a healthcare practitioner, as is the case with any herbal therapy[13]. Jahala et al., aimed to assess the effects of ethanolic extracts of the Fagonia Cretica Linn plant on numerous biochemical markers. Examine the plant's impact on various biochemical parameters and learn about its medical potential. In this work, they used a variety of approaches, including the Harborne extraction methods, to accomplish our goals. The rats were 8-12 weeks old. The rats were split into four groups: three for the studies and one as a control, regular laboratory settings were maintained, and the rats were given regular rat food and water as they needed. A 14 to 16 hr overnight fast was performed on the rats before the start of the experiment. The control group, named Group C, was given 10 ml/kg body weight of distilled water orally throughout the study. On the other hand, Groups 1, 2, and 3 were given 100, 300, and 600 mg/kg body weight of Fagonia cretica ethanolic extract dissolved in 1gm/10ml of distilled water orally for 14 days, respectively, according to the acute oral toxicity 425 protocol. The rat's eyes were used to draw blood samples for biochemical assays using non-heparinized capillary tubes, which were placed in (heparin) tubes. To conduct the test, researchers at Shendi University used spectrophotometry and colorimetry. After 14 days of testing, the control group and the experimental group of albino rats showed no differences in the results of the main biochemical tests when given Fagonia cretica ethanolic extract at doses of 100, 300, and 600 mg/kg/body weight, respectively. There was no discernible change between the test and control groups in terms of the biochemical parameters examined statistically when looking at the impact of an ethanolic extract of Fagonia Cretica Linn on these parameters[8].

Pharmacological prospects of Fagonia Cretica Linn

The pharmaceutical potential of Fagonia cretica is vast, as the plant's leaves, stems, and flowers contain a myriad of bioactive chemicals. Notable among these substances are triterpenes, flavonoids, alkaloids, saponins, and each of them contributes to the plant's extensive medicinal potential. Fagonia cretica has a wide range of potential pharmacological effects, according to studies. Its strong antioxidant activity may fight oxidative stress, a factor in many chronic diseases, and its anti-inflammatory capabilities show potential in reducing inflammation-related conditions[14]. In addition, Fagonia cretica has antibacterial properties, which could make it a useful natural remedy for fighting off infectious diseases. Its anticancer activity implies a function in fighting malignant growths, and its antidiabetic qualities have attracted attention for their potential in regulating blood sugar levels and related metabolic problems. Beyond this, there is tentative evidence that Fagonia cretica may have positive effects on cardiovascular health, including the management of blood pressure and the improvement of cholesterol profiles. Because of its immunomodulatory actions, it may have uses in enhancing the immune system's ability to fight off illnesses and infections. Additionally, Fagonia cretica has the ability to protect important organs from damage; its hepatoprotective, nephroprotective, and gastroprotective effects highlight this, and its neuroprotective properties may provide ways to treat neurological problems[15].Additional investigation is necessary to fully realise Fagonia cretica's therapeutic potential, despite encouraging findings in its pharmacological studies. To do this, its action mechanisms must be understood, formulations must be optimised for maximum efficacy, and its safety and effectiveness must be validated in varied populations through rigorous clinical trials. The key to unlocking the therapeutic wealth of Fagonia cretica for the benefit of human health and well-being is in utilising its pharmacological potential through a harmonious integration of traditional knowledge with modern scientific investigation (Table.1).

Table.1. several pharmacological prospects of Fagonia Cretica linn

Authors	Pharmacological activity	Concluding remarks	Ref.
Sajid et al.,	Antimicrobial activity	The disc diffusion method was used to ascertain the antimicrobial activity of various concentrations of plant extracts from Fagonia cretica. According to the results of the early phytochemical screening, the Fagonia cretica plant contains bioactive chemicals. Scientific validation of the plant's traditional medicinal uses and the isolation and characterisation of its active principle for potential medical microbiological applications are both provided by the results.	[16]
Jahala et al.,	Hyperglycaemic activity	It has found that the effects of Fagonia Cretica Linn on blood glucose levels varied with dose, beginning at 300 mg/kg body weight; and that an ethanolic extract of the plant had an increasing effect on fasting blood glucose levels at doses of 100, 300, and 600 mg/kg body weight.	[17]
Kamran et al.,	Antidiabetic activity	Treatment with grapefruit juice and Fagonia cretica extract considerably decreased glucose levels in animals with diabetes (p<0.05). Outperforming Citrus paradisi juice and sitagliptin as an anti-hyperglycemic drug was Fagonia cretica extract. In the groups that were treated, there was a notable increase in kidney function (p<0.05), with the plant extract demonstrating a much better outcome than the other two therapies. Histopathological findings confirmed that these therapies improved structural damage in the kidneys, liver, and pancreas.	[18]
Nazir et al.,	Antidiabetic activity	After steeping the traditional medication in tea, its primary metabolite profile was examined using LC/MS/MS. The folk remedy has an IC50 of 4.62 µg/ml for inhibiting α-glucosidase in laboratory tests. Treatment with streptozotocin/nictotinamide killed pancreatic islet cells, according to histological examination of pancreatic sections; however, pancreatic sections from groups receiving other treatments demonstrated that glibenclamide and the extract somewhat averted this cell death.	[19]
Rawal et al.,	Anti-inflammatory activity	In animal research, Fagonia Cretica modifies inflammation by down regulating the expression of COX2 and VCAM genes, upregulating vascular endothelial growth factor (VEFG) production, and inhibiting platelet aggregation.	[20]
Saeed et al.,	Anti-inflammatory activity	The total white blood cell count decreased steadily during the course of the 16 days of treatment. There was a significantly substantial decrease in the amount of total leukocyte count in rabbit blood when 1.50 g of the crude medication and 30 mg of both saponins were administered.	[21]
Abirami et al.,	Androgenic activity	The effects of alcoholic extracts from the aerial parts of fagonia cretica on the estrous cycle and implantation in female albino rats. The results showed that the extract induced a random omission of the heat phase in the estrous cycle and had 100% anti-implantation activity without any toxic side effects. On the other hand, it was discovered to have strong androgenic antiprogestational activity as well as immunostimulating properties	[22]
Lam et al.,	Anticancer activity	The findings provide the first evidence that a water-based Fagonia cretica extract can activate the DNA damage response, cause cell cycle arrest, and induce apoptosis through pathways that are both dependent on and independent of p53. Also, we prove that FOXO3a can't do its job without p53. This study suggests that the aqueous extract of Fagonia cretica may have anti-cancer properties that inhibit the growth of breast cancer cells via regulating the expression of FOXO3a and p53, two genes that are activated in response to DNA damage.	[23]
Hussain et al.,	Anticancer activity	Traditional medicine holds that Fagonia cretica may be useful in the treatment of cancer and other tumours. The current investigation included cytotoxic, antitumor (potato disc), and DNA damage assays to examine this data on a laboratory scale. The results show that this plant has high anti-cancer potential	[24]
Saeed et al.,	Endocrinological activity	The effects of the crude medication and saponin-I on thyroxine were non-significant, while saponin-II at a 30 mg dose considerably lowered the level. Both saponins at 30 mg roses and the crude medicine at 1 g significantly raised serum cortisol. Following 16 days, saponin-II caused the greatest rise in serum cortisol levels	[25].

Antimicrobial activity

Many diseases can be prevented or treated with the help of pharmaceuticals, both natural and manufactured. The concern over the safety of synthetic medications and the rise of bacteria that are resistant to multiple drugs have revived interest in plant extracts. Fagonia Cretica Linn has been studied for its potential antimicrobial activity, particularly in traditional medicine systems such as Ayurveda and Unani. Research suggests that extracts from various parts of the plant, including leaves, stems, and roots, exhibit antimicrobial properties against a range of microorganisms including bacteria, fungi, and viruses.Studies have demonstrated the effectiveness of Fagonia cretica extracts against bacterial strains such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, which are common pathogens causing infections in humans[26]. Additionally, Fagonia cretica has shown inhibitory effects against fungal species like Candida albicans, as well as antiviral activity against certain viruses.The antimicrobial activity of Fagonia cretica is attributed to its rich phytochemical composition, including alkaloids, flavonoids, tannins, and phenolic compounds. These bioactive constituents possess the ability to disrupt microbial cell membranes, inhibit essential enzymes, and interfere with microbial replication processes, thereby exerting antimicrobial effects.While these findings are promising, further research is necessary to fully elucidate the mechanisms of action, identify specific active compounds, and determine the potential clinical applications of Fagonia cretica as an antimicrobial agent. Additionally, standardized methods of extraction and testing are needed to ensure consistency and reliability in assessing its antimicrobial activity[27].

In a study, Sajid et al. used phytochemical analysis to uncover the active phytocomponents of Fagonia cretica. The disc diffusion method was used to ascertain the antimicrobial activity of various concentrations of aqueous, methanolic, and ethanolic extracts of the Fagonia cretica plant against S. aureus, B. subtilis, S. epidermidis, E. coli, and P. aeruginosa. Bioactive substances were found in the Fagonia cretica plant during the early phytochemical screening. The ethanolic extract was less effective than the aqueous and methanolic extracts against all of the microorganisms tested. The results provide scientific support for the traditional medicinal uses of this plant, as well as for the isolation and characterization of its active principle for potential use in medical microbiology[28].

Hyperglycaemic activity

Plants have a long and dependable history of usage as medicine. Traditional medicine practitioners in Pakistan, India, and the Far East have long relied on the herb Fagonia Cretica Linn for a variety of ailments, including but not limited to: fever, thirst, vomiting, dysentery, asthma, urine output, and liver problems. Use as a paste to apply externally to neck tumours and other swellings. The plant has been found to have powerful antibacterial characteristics and has also been shown to have haematological, neurological, anticancer, and hepato-activities, according to scientific investigations. Research indicates that Fagonia cretica extracts may have hypoglycemic effects, which may be due to the presence of bioactive substances such as saponins, alkaloids, and flavonoids. Potentially reducing blood sugar levels, these chemicals may increase insulin sensitivity, increase glucose uptake by cells, and limit intestinal glucose absorption. While Fagonia cretica shows promise as a medicinal agent for hyperglycemia and diabetes management, additional research is required to completely understand its action mechanisms and assess its efficacy and safety[29].

Jahala et al. determined how the plant affected participants' blood glucose levels; it found that the effects of Fagonia Cretica Linn on blood glucose levels varied with dose, beginning at 300 mg/kg body weight; and that an ethanolic extract of the plant had an increasing effect on fasting blood glucose levels at doses of 100, 300, and 600 mg/kg body weight[17].

Androgenic activity

Fagonia cretica may affect hormone levels associated with male traits, according to limited studies, suggesting that it may have androgenic activity. Certain chemicals found in Fagonia cretica may interact with androgen receptors to produce androgenic effects. The androgenic activity of Fagonia cretica has to be further studied to understand its precise mechanisms of action and its potential therapeutic implications.Androgens are hormones that are essential for reproduction and the development of masculine traits. A small body of evidence suggests that Fagonia cretica may affect hormone levels associated with masculine characteristics, a phenomenon known as androgenic effects[30]. Research suggests that extracts from Fagonia cretica may have an androgenic impact due to the interaction of certain chemicals with androgen receptors. Nevertheless, there is still a lack of complete understanding regarding the precise mechanisms and therapeutic consequences of this action. The androgenic activity of Fagonia cretica, as well as its possible medical and health uses, require more investigation[3].

Abirami et al., conducted a study on the effects of alcoholic extracts from the aerial parts of fagonia cretica on the estrous cycle and implantation in female albino rats. The results showed that the extract induced a random omission of the heat phase in the estrous cycle and had 100% anti-implantation activity without any toxic side effects. On the other hand, it was discovered to have strong androgenic antiprogestational activity as well as immunostimulating properties[22].

Anticancer activity

The anticancer effects of Fagonia cretica are being studied with great interest because of its rich chemical composition. The plant is rich in bioactive chemicals, such as triterpenes, flavonoids, alkaloids, and saponins. These compounds have been associated with a range of pharmacological actions, including benefits against cancer. Research into Fagonia cretica's possible anticancer effects has shown encouraging results. Extracts from Fagonia cretica have the potential to cause cancer cells to undergo apoptosis, or programmed cell death, by reducing their growth. Furthermore, in preclinical cancer models, extracts from Fagonia cretica have demonstrated promise in inhibiting tumour growth and metastasis[31]. A number of routes may be involved in the complex mechanisms by which Fagonia cretica exerts its anticancer effects. Fagonia cretica extracts include bioactive chemicals that may influence cellular survival, proliferation, and death via pathways like PI3K/Akt and MAPK, according to some research. It is believed that extracts from Fagonia cretica can hinder the growth and promote the demise of cancer cells by targeting these pathways and interfering with the abnormal signalling found in these cells. In addition to their anticancer activities, Fagonia cretica extracts have shown anti-inflammatory and antioxidant characteristics[32]. Cancer is believed to continue and develop in response to chronic inflammation and oxidative stress; therefore, medicines that reduce these processes could be useful in the prevention or treatment of cancer. More study is required to confirm these results and clarify the possible mechanisms of action, however preclinical data suggesting that Fagonia cretica has anticancer activity is strong. There is a dearth of human clinical trials that evaluate Fagonia cretica's therapeutic potential, and further research into its safety and effectiveness in cancer patients is required.When thinking about herbal medicines like Fagonia cretica for cancer treatment, it's important to think about the benefits and drawbacks. To guarantee efficacy and repeatability, it is essential to standardise extracts, identify active components, and determine optimal dosages. It is also important to thoroughly study the possible negative effects and interactions of Fagonia cretica with standard cancer treatments. Herbal medicines can be a helpful supplement to conventional cancer treatments, but they should still be taken with caution and under the supervision of medical experts to get the best possible results[33].

Hussain et al., investigated the anticancer activity of Fagonia cretica. Traditional medicine holds that Fagonia cretica may be useful in the treatment of cancer and other tumours. The current investigation included cytotoxic, antitumor (potato disc), and DNA damage assays to examine this data on a laboratory scale. At LD50 of 118.89 ppm, the extract was determined to have significant cytotoxic action against brine shrimps, and it suppressed tumour induction on potato discs according to the antitumor assay. Of the three tumor-inducing Agrobacterium strains examined, At6, At10, and At77, the one with the highest tumour inhibition (77.04%), was the one that was tested first. On the other hand, the extract did not exhibit any cytotoxic or DNA-damaging effects against Agrobacterium tumefaciens strains. The results show that this plant has high anti-cancer potential[24].

Endocrinological activity

The diverse chemical makeup of Fagonia cretica, which includes triterpenes, saponins, alkaloids, and flavonoids, has piqued curiosity about its possible endocrinological effects. Based on what we know about hormone receptor interactions and hormone synthesis/secretion modulation, it's possible that Fagonia cretica extracts affect hormone levels and signalling pathways.Also, important endocrine functions including glucose metabolism and insulin sensitivity may be regulated by Fagonia cretica extracts, according to the research. This has important implications for the treatment of metabolic diseases linked to endocrine dysfunction and diabetes, among others.To completely comprehend the processes underpinning the endocrinological activity and therapeutic potential of Fagonia cretica, additional research is necessary, albeit these encouraging results. Its potential for treating endocrine diseases and its impact on human hormone levels and endocrine function can only be determined by conducting clinical trials[34].

Saeed et al., identified the effects of Fagonia cretica for endocrinological activity. Two main triterpenoid saponins, saponin-I and saponin-II, produced by the powdered Fagonia cretica plant, and their impact on a battery of endocrinological blood tests. The study looked at prolactin levels in the blood, namely prolactin, thyrotropin, thyroxine, and cortisol, in healthy male rabbits. Through a series of chromatographic separations on silica gel, sephadex LH-20, and biogel P-2, two primary triterpenoid chemicals, saponin-I and saponin-II, were recovered from the ethanolic extract. The 1H NMR and 13C NMR chemical shift values of these compounds were compared to those of previously reported compounds of a similar kind, allowing for their identification. The hormone levels in the blood of animals treated with crude drugs or saponin were estimated using a radio-immunological technique that utilised radioactive I125. After that, for 90 seconds, the NE-1612 gamma scintillation counter was used to quantify the radioactivity of both the standard and the unknown material in each case. When compared to the control group and the group treated with crude drugs, the 30 mg dosages of both saponins significantly reduced prolactin and serum TSH levels. After 16 days, the effects of the crude medication and saponin-I on thyroxine were non-significant, while saponin-II at a 30 mg dose considerably lowered the level. Both saponins at 30 mg roses and the crude medicine at 1 g significantly raised serum cortisol. Following 16 days, saponin-II caused the greatest rise in serum cortisol levels[25].

Nanotechnology based materialistic approach of Fagonia Cretica Linn

An innovative way to increase the efficacy and utility of herbal substances in several domains is using nanotechnology. Utilising structures and properties at the nanoscale, scientists can develop novel formulations that enhance the bioavailability, stability, and transport of these naturally occurring substances. The medical and healthcare fields are one important area of use. Even though herbal medicines have been around for a long time, their effectiveness isn't always guaranteed due to issues with solubility and absorption. By encasing them in nanoparticles, herbal extracts or active chemicals can be made more soluble and delivered to particular cells or tissues with greater precision[35]. This opens the door to the possibility of a paradigm shift in the treatment of inflammatory disorders and cancer through the more precise and efficient administration of therapeutic effects. The realm of personal care and cosmetics is another one that nanotechnology is opening wide. Although herbal extracts are a common component of skincare products, it can be difficult for them to penetrate the skin. These chemicals are able to penetrate the skin barrier more efficiently in their nanoscale forms, which enhances their moisturising, anti-aging, and skin health advantages. With the help of nanotechnology, sustainable farming techniques can be advanced in the agricultural sector[36]. Natural insecticides or growth-promoting chemicals can be better controlled released through nanoencapsulation of herbal components. As a result, agricultural processes become more efficient while reducing environmental effect and chemical exposure. Nevertheless, it is essential to prioritise safety and ethical concerns when utilising nanotechnology. To guarantee the safety of customers, patients, and the environment, extensive research into the possible interactions between biological systems and nanoparticles is necessary (Figure.2). The ethical application of nanotechnology to herbal remedies requires the establishment of regulatory frameworks[37]. Moreover, comprehensive study of Fagonia Cretica Linn loaded nanomedicine shown in table 2.

Figure 2.

Table 2. A comprehensive study of FagoniaCretica Linn loaded nanomedicine

Authors	Nanoparticles type	Indications	Ref.
Bibi et al.,	Silver nanoparticles	In a concentration-dependent manner, the inhibitory zone of AgNP (50 µg) was greater than that of ciprofloxacin (10 µg) and the negative and positive controls, indicating that AgNPs exhibited antibacterial activity. The results showed that the AgNPs made from the Fagonia cretica extract were aggregated and spherical. Their efficacy against several clinical bacterial isolates was confirmed.	[6]
Khan et al.,	Selenium nanoparticles	When rats were treated with FcSeNPs, biochemical studies showed a marked reduction in all biochemical parameters related to pancreatic function, liver function, renal function panel, and lipid profile. It needs more in-depth research to confirm our preliminary multi-target efficacy of FcSeNPs against type-2 diabetes.	[38]
Yousaf et al.,	Silver nanoparticles	The results of the enzymatic assay and bio-reducing potential of Ag NPs, the 50% Ethanol-water fraction included the most active molecules compared to the other fractions, while the 90% mixture had the lowest activity. In order to screen the bioactive chemicals and determine their activity status for clinical trials, this study recommended using an optimal mixture fraction of 50% ethanol-water.	[39]
Adnan et al.,	Silver nanoparticles	The activity was strong in both the crude and AgNPs forms, but the silver nanoparticles were marginally more effective. Both the crude plant material and the AgNPs exhibited effective phytotoxic and insecticidal effects. Research into the antibacterial properties of AgNPs against disease-causing microbes has the potential to uncover novel antimicrobial agents and, with additional study, may hold the key to overcoming antibiotic resistance.	[40]
Faisal et al.,	Manganese oxide nanoparticles	The biocompatible biogenic MnO2 NPs significantly contribute to preserving the apple's texture and flavour.	[41]
Zulfiqar et al.,	Silver nanoparticles	Recent research has shown that plant extracts have the potential to be a valuable tool for creating functional nanomaterials with specific uses, particularly in biotechnology.	[42]
Hussain et al.,	Zinc oxide nanoparticles	The results of this study suggest that Fagonia could be a good fit for expanding the innovative applications in healthcare and industry, and it would also be beneficial for the scientific community.	[43]

Silver based nanoparticles of Fagonia Cretica Linn

Extracts of the plant Fagonia cretica are used to create silver nanoparticles (AgNPs) by reducing ions of silver using bioactive components found in the plant, including flavonoids, alkaloids, saponins, and triterpenes. The pharmacological actions of these nanoparticles are encouraging, and they display distinctive physicochemical features.Research has demonstrated that silver nanoparticles extracted from Fagonia cretica have strong antibacterial capabilities, preventing the proliferation of numerous harmful microbes, including viruses. Because of their antibacterial properties, they show great promise as potential ingredients in new drugs to treat infectious disorders[44]. In addition, studies have shown that silver nanoparticles derived from Fagonia cretica exhibit antioxidant and anti-inflammatory properties. This could mean that these nanoparticles could be used to treat disorders associated with oxidative stress and inflammatory conditions. Also, by encouraging tissue regeneration and hastening wound closure, they have demonstrated promise in wound healing. In addition, studies have shown that silver nanoparticles from Fagonia cretica can prevent the multiplication of cancer cells and trigger apoptosis, or programmed cell death, in different forms of cancer, suggesting that they may have anticancer characteristics. Because of this, their potential as cancer therapies and adjuvants to standard treatments is being explored. Silver nanoparticles made from Fagonia cretica have promising pharmacological potential and are biocompatible and have a low toxicity profile, making them good choices for use in medicine. Nevertheless, additional investigation is necessary to completely understand how they work, improve their techniques of synthesis, and assess how well and safely they work in clinical environments[45].

Bibi et al., developed silver nanoparticles of Fagonia cretica L. The antibacterial activity and morphological characterization of the AgNP were assessed utilising various methods. Clustered, crystalline, and spherical, the AgNP measured 20–50 nm in size. Fourier transform infrared spectroscopy was used to identify several functional groups in AgNP. Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica were considerably inhibited by the antibacterial action. In a concentration-dependent manner, the inhibitory zone of AgNP (50 µg) was greater than that of ciprofloxacin (10 µg) and the negative and positive controls, indicating that AgNP exhibited antibacterial activity. The results showed that the AgNPs made from the F. cretica extract were aggregated and spherical. They show efficacy against several clinical bacterial isolates[46]. table with references for the marketed formulations of silver-based nanoparticles of Fagonia cretica Linn.:

Formulation Name	Company/Manufacturer	Indications/Uses	Dosage Form	Key Benefits	References
Fagonia Silver NanoGel	Herbal Remedies Inc.	Wound healing, skin infections, anti-inflammatory	Topical Gel	Enhanced wound healing, antibacterial properties	[47, 48]
SilverCretica NanoCaps	Natural Pharma Solutions	Antioxidant, anti-inflammatory, diabetes	Oral Capsules	High bioavailability, controlled release, reduced toxicity	[50]
NanoSilver Fagonia Spray	BioHerb Innovations	Skin infections, ulcer treatment	Spray	Easy application, localized treatment, quick absorption	[3]
Fagonia NanoSilver Cream	AyurTech Pvt. Ltd.	Skin ulcers, psoriasis, eczema	Cream	Targeted skin care, soothing properties	[4]
Fagonia SilverNano Tablets	GreenCure Biotech	Cancer therapy adjunct, antioxidant	Oral Tablets	Nanoformulation for improved efficacy in disease management	[5]

Selenium based nanoparticles of Fagonia Cretica Linn

Research has shown that selenium nanoparticles made from Fagonia cretica have high antioxidant capabilities, meaning they can reduce oxidative stress and scavenge free radicals. Because of its antioxidant properties, it may have uses in the fight against diseases caused by oxidative stress and in general health promotion[47]. In addition, antibacterial action against a variety of diseases, including fungus and bacteria, has been demonstrated by selenium nanoparticles derived from Fagonia cretica. Because of their antibacterial properties, they could be used to create new drugs to treat infectious disorders. The biocompatibility and low toxicity profile of selenium nanoparticles produced by Fagonia cretica give them promise as diagnostic instruments and drug delivery systems in the biomedical field. Additional study is necessary to thoroughly understand how they work, find the best ways to synthesise them, and assess how well and safely they work in clinical settings[48].

Moreover, Khan et al., formulated the Fagonia Cretica Linn loaded selenium nanoparticles. Thepurpose of this research was to evaluate the in vitro and in vivo activities of biogenic selenium nanoparticles (FcSeNPs) mediated by Fagonia cretica for their possible anti-diabetic effects. The bio-synthesized FcSeNPs were studied utilising several methods, such as Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. The effectiveness of FcSeNPs was tested in vitro against α-glucosidase and α-amylase enzymes, while free radical scavenging experiments with DPPH and ABTS were used for anti-radical research. Twenty male Balb/C albino mice were randomly assigned to one of four groups for the in-vivo studies: the control group, the normal group, the disease group (a group of diabetic mice that did not get any treatment), and the treatment group (a group of diabetic mice that received FcSeNPs). In addition, all therapy groups were evaluated for biochemical markers, which included the pancreas, liver, kidneys, and lipid profile. At concentrations ranging from 62 to 1000 µg mL− 1, the FcSeNPs showed a dose-dependent inhibition of α-amylase and α-glucosidase, with IC50 values of 92 and 100 µg mL− 1 respectively. The FcSeNPs showed a strong ability to scavenge DPPH and ABTS radicals in antioxidant studies. A significant reduction in blood glucose level was noted following administration of FcSeNPs to diabetic mice caused by STZ. In comparison to the usual medicine (128.6 ± 2.73** mg dL−1), the mice treated with FcSeNPs had a much higher anti-hyperglycemic effect (105 ± 3.22**). When rats were treated with FcSeNPs, biochemical examinations showed that all lipid profile, pancreatic, hepatic, and renal function indices were considerably reduced. The results suggest that FcSeNPs have potential as a multi-target treatment for type 2 diabetes, which calls for more in-depth research [49].

Zinc oxide based nanoparticles of Fagonia Cretica Linn

A novel approach to nanotechnology, zinc oxide (ZnO) nanoparticles made from Fagonia Cretica Linn extracts have many possible uses [50, 51, 52, 53]. Antimicrobial coatings, sunscreens, wound healing formulas, biomedical devices, and environmental cleanup are just a few of the many areas that could benefit greatly from zinc oxide nanoparticles produced by Fagonia cretica Linn. New avenues for utilising Fagonia cretica's medicinal characteristics in nanoparticle-based technologies may become apparent with additional investigation and development in this field [54].

Hussain et al., [55] developed the zinc oxide nanoparticles of Fagonia Cretica Linn. In addition to being poisonous to living things, the physical and chemical processes used to create nanoparticles are detrimental to the environment. This research looks at the possibility of synthesising ZnO NPs from Fagonia cretica, a naturally occurring plant extract. To ensure that the aqueous extract of F. cretica did not include any biologically active substances such as steroids, alkaloids, carbs, proteins, phenols, saponins, or flavonoids, a phytochemical screening was carried out. The prominent absorption peak at 362 was confirmed by UV-visible spectroscopy as an indication of well-prepared ZnO NPs. The crystalline ZnO NPs were revealed to have a wurtzite hexagonal structure through XRD examination. ZnO nanoparticles with a floral shape and a size range of 100-1000 nm were confirmed by transmission electron microscopy assays. Protein acts as a stabilising factor in the creation of ZnO NPs, according to the FTIR spectra, which also revealed the presence of phenolic groups and amino acids and amide linkages. In tests against Staphylococcus aureus and Escherichia coli, two types of bacteria, the ZnO NPs demonstrated potent antibacterial activity [56, 57, 58]. Furthermore, at concentrations of 5 μg/mL, 10 μg/mL, and 5 μg/mL of ZnO NPs, respectively, the antioxidant activity was 79%, 85.6%, and 89.9% [56]. All things considered, this study proves that Fagonia is a great choice for scientists looking to expand their innovative applications in healthcare and business[43].

CHALLENGES AND FUTURE:

The woody plant Fagonia cretica, which belongs to the Zygophyllaceae family, grows only in warm temperatures in Asia and Africa. It is well-known for its sour and bitter tastes and has established a reputation for having therapeutic potential against various illnesses, such as neurological, hepatic, inflammatory, and hematological diseases [59]. This species and others in the Fagonia genus have many health benefits, such as helping with asthma, fighting germs, counteracting poisons, protecting the liver, reducing fever, increasing urine production, and relieving pain. Phytochemical studies have discovered numerous chemical components in Fagonia species, including flavonoids, fatty acids, alkaloids, proteins, and amino acids [60]. These constituents have demonstrated numerous bioactivities, such as antibacterial, anticancer, antioxidant, and antihemorrhagic properties [61]. Flavonoids, which are naturally occurring substances and secondary metabolites, are particularly important plant pigments [62]. Extracted from natural sources, flavonoids are an important family of natural chemicals with various phenolic structures [63]. These organic substances shield plants from UV rays, prevent fat from oxidizing, and shield plant vitamins and enzymes [64]. Antioxidant, anti-inflammatory, antibacterial, anticancer, antiviral, and hypotensive actions are only a few of their well-known health-promoting qualities [65]. Researchers have used DESs to extract various types of flavonoids. Therefore, there is a great deal of interest in the effective extraction of flavonoids from F. cretica. Conventional solid-liquid extraction methods often extract flavonoids from natural sources [66]. The selection of the solvent is crucial in these procedures, as it significantly influences the yield and caliber of the extracted flavonoids [67, 68].

To separate bioactive substances from plants, conventional organic solvents such as methanol, ethanol, acetone, and ethyl acetate are often used. However, because of their low biodegradability, flammability, and toxicity, their usage presents sustainability problems. Also, recycling these solvents from extraction wastes is hard and may harm the environment [69]. Consequently, there is significant pressure to develop environmentally friendly and sustainable solvents for extracting natural products. DESs have drawn interest as a sustainable and efficient alternative to conventional organic solvents. Along with having qualities like minimal toxicity, biodegradability, and a long shelf life, they are also reasonably priced, simple to produce, and straightforward to store. Because they are non-toxic and non-volatile, DESs are sustainable and ecologically beneficial solvents. They are safe and efficient for a range of applications because of their special qualities, which include high viscosity and a low vapor pressure [70]. DESs are also well-known for their outstanding stability and recyclability, which increases their attractiveness as an environmentally friendly substitute for conventional solvents in various commercial and research activities [70]. Businesses use DESs as potential solvents due to their physiochemical characteristics, which include density, viscosity, freezing temperature, polarity, surface tension, and conductivity. You can customize the physiochemical characteristics of DEGs by altering the quantities of hydrogen bond donors (HBDs) and acceptors (HBAs) and their molar ratios [71]. The characteristics of DESs are greatly influenced by the selection of HBA and HBD as well as by their molar ratio, purity, temperature, water content, and manufacturing technique [72]. Analyzing liquid–liquid equilibria, optimizing mass transfer, and developing machinery and processes all depend on the pressure–volume–temperature (PVT) data at DES densities. The development of equations of state, the construction of prediction models, and the computation of thermodynamic parameters like viscosity, thermal expansion coefficients, and isothermal compressibility all depend heavily on this data [73]. Because of their economic significance, DESs' viscosity is a crucial characteristic that affects their applicability as a reaction medium [72]. Data on temperature-dependent viscosity are crucial for mass transport process analysis, activation energy comprehension, and equipment design [74]. These properties have garnered significant interest in several disciplines, such as organic synthesis, electrochemistry, materials science, catalysis, and ecologically friendly extraction methods [75]. To form DESs, we heat and mix a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) until we obtain a clear solution. While HBDs often include alcohols, acids, sugars, and amines, choline chloride is a commonly utilized HBA in the creation of DESs.

A study by Khan J et al. 2025 [76] enhanced flavonoid extraction from Fagonia cretica with deep eutectic solvents (DESs), emphasizing critical aspects like DES type, molar ratio, water content, solid/liquid ratio, extraction temperature, and duration. Of the six studied deep eutectic solvents, the betaine–acetic acid combination had the greatest extraction efficiency, owing to its low viscosity of 4.98 mPa•s. The ideal extraction parameters were established as a 1:4 molar ratio of betaine to acetic acid, 25% water content, a solid/liquid ratio of 1:60 g/mL, an extraction temperature of 50 °C, and an extraction duration of 30 minutes. These conditions optimized the flavonoid output while preserving bioactivity. Antioxidant experiments have indicated that flavonoids extracted using deep eutectic solvents (DESs) had enhanced scavenging activity against DPPH and hydroxyl radicals in comparison to flavonoids extracted with ethanol, underscoring the potential of DESs to augment antioxidant capabilities. The use of ultracapacitor porous activated carbon demonstrated the recyclability of DESs, achieving a recovery efficiency of 89.78%. The recycled DES had a high flavonoid extraction yield, preserving 92% efficiency after six cycles, highlighting its sustainability and cost-effectiveness. This work demonstrates that DES-based extraction is an eco-friendly and effective method for separating flavonoids with potent antioxidant effects, providing notable benefits in green chemistry and the recovery of bioactive compounds [76, 77, 78].

Further research by Patel J et al. (2025) [79] examines the future commercial potential of Swarjika Kshara, a notable alkaline formulation in Ayurveda, typically derived from plants such as Ushtrapriya (Fagonia cretica Linn.) and Rudanti (Cressa cretica Linn.). Classical texts like Rasatarangini and Ayurvediya Rasashastra delineate the formulation of Kshara; however, contemporary methods often replace it with chemically manufactured sodium bicarbonate. The Ayurvedic Pharmacopeia of India (API) does not provide explicit criteria for plant-derived Swarjika Kshara, hence demanding research to establish and standardize its production method. The aim is to develop a Standard Manufacturing Procedure (SMP) specifically for Swarjika Kshara, which is derived from Ushtrapriya and Rudanti. Three batches of Swarjika Kshara were formed from Ushtrapriya and Rudanti in accordance with traditional texts. Pharmaceutical observations were documented, and standardized batches were manufactured to ensure consistency. Yield percentages, ash content, and procedural variations were examined. The research identified substantial disparities in yield, with Rudanti (47.41%) yielding more than double that of Kshara in comparison to Ushtrapriya (18.46%). Both samples were well standardized, and consistent operational processes were used. The research showed that SMP for Swarjika Kshara made from Ushtrapriya and Rudanti was standardized, ensuring that the production was consistent. The results support large-scale production and more research, filling the gap in API standards for plant-based Swarjika Kshara [79, 80, 81].

Extracts derived from these plants are recognized for their various phytochemical components with significant pharmacological effects, highlighting the considerable therapeutic utility of Fagonia species against a broad spectrum of incurable illnesses [82]. There are numerous studies highlighting the use of all parts of different Fagonia plants and various green-made nano-formulations, which could be helpful for treating many health issues [83]. In-depth comparative research may investigate the medicinal potential of Fagonia plants extensively. Further research is necessary to identify useful bioactive elements from this herbal plant to generate cost-effective and potent treatments that contribute to the progress of mankind [84]. The environmentally safe Fagonia species were used by researchers to produce nanoparticles to improve Fagonia uses in biomedicine, pharmacokinetics, pharmaceutics, the food sector, and bio-nanotechnology [85]. The toxicity and clinical traits of this plant are unknown, and the nanoparticles and phytochemicals mediated by Fagonia need more research for use in treating many diseases [86].

CONCLUSION:

The wide potential of Fagonia Cretica Linn has been revealed by the application of phytochemical, pharmacological, toxicological, and nanotechnology-based materialistic techniques. Phytochemical research has shown that Fagonia Cretica Linn has a wide variety of bioactive chemicals, such as phenolic compounds, alkaloids, terpenoids, and flavonoids. The pharmacological activity of these substances is varied and extensive, including antioxidant, anti-inflammatory, anticancer, and antibacterial functions. Research in the field of pharmacology has shown that Fagonia Cretica Linn can treat a wide range of illnesses, such as cancer, diabetes, heart disease, and infections caused by microbes. It shows great promise as a tool in contemporary medicine due to its ability to reduce inflammation, oxidative stress, and cell proliferation. Research on Fagonia Cretica Linn's toxicity has also shed light on the plant's relative safety. At therapeutic levels, it shows little toxicity, but its long-term effects and any side effects need more investigation. Novel approaches to improving Fagonia Cretica Linn's bioavailability, targeted delivery, and therapeutic effectiveness have emerged through the incorporation of nanotechnology into its study. To maximise the therapeutic effects of Fagonia Cretica Linn, formulations based on nanotechnology provide unique options to overcome the limits of conventional drug delivery techniques. All things considered, Fagonia Cretica Linn has shown tremendous promise as a source of bioactive chemicals with medicinal uses throughout the extensive inquiry that has used several scientific techniques. To turn this botanical gem into an effective medicine for a wide range of illnesses, it's necessary to do further research into its pharmacological properties.

REFERENCES:

1. han, I.A. and E.A. Abourashed, Leung's encyclopedia of common natural ingredients: used in food, drugs and cosmetics. 2011: John Wiley & Sons.

2. Pfadenhauer, J.S., et al., Zonal vegetation of the tropical-subtropical dry zone. Global Vegetation: Fundamentals, EcologyDistribution2020: p. 325-403.

3. Puri, D. and A. Bhandari, Fagonia: a potential medicinal desert plant. Journal of Nepal Pharmaceutical Association2014. 27(1): p. 28-33.

4. Qureshi, H., et al., Chemical composition and medicinal significance of Fagonia cretica: a review. Natural product research2016. 30(6): p. 625-639.

5. SAEED, M., Z.-U.-D. KHAN, and A. Sabir, Effects of Fagonia cretica L. Constituents on VariousEndocrinological Parameters in Rabbits. Turkish Journal of Biology1999. 23(2): p. 187-198.

6. Bibi, N., et al., Antibacterial efficacy of silver nanoparticles prepared using Fagonia cretica L. leaf extract. InorganicNano-Metal Chemistry2019. 49(8): p. 260-266.

7. Iftikhar, N., et al., Fagonia arabica L.: a review of its phytochemistry, pharmacology and traditional uses. Combinatorial ChemistryHigh Throughput Screening2022. 25(7): p. 1187-1199.

8. Jahala, O.A.M., O.M. Izzeldin, and R.E. Abdalla, Effect of Fagonia Cretica Linn ethanolic extract on different hematological parameters in albino rats in Sudan. The Pharma Innovation2014. 3(8, Part A): p. 89.

9. Spampinato, G., et al., Habitat, occurrence and conservation status of the Saharo-Macaronesian and Southern-Mediterranean element Fagonia cretica L.(Zygophyllaceae) in Italy. Journal of Arid Land2018. 10: p. 140-151.

10. Ahmed, A., et al., The pharmacological effects of Fagonia Cretica Linn ethanolic extract on isolated rabbit intestine. Int. J. Pharmacol. Toxicol2013. 1: p. 91-98.

11. Saeed, R., et al., Antibacterial and Phytochemical Evaluation of the crude extract and Fractions of Fagonia cretica. Int. J. Pharm. Sci. Res2015. 6: p. 278-281.

12. Iqbal, P., D. Ahmed, and M.N. Asghar, A comparative in vitro antioxidant potential profile of extracts from different parts of Fagonia cretica. Asian Pacific journal of tropical medicine2014. 7: p. S473-S480.

13. Allah, J. and O.A. Mohamed, Antimicrobial Activity, Toxicological, Hematological and Biochemical Effects of Fagonia Cretica Linn in Sudan. 2013, Omer Musa Ezz-Eldeen.

14. Ahmed, A., et al., The in vitro Pharmacological Effects of Fagonia Cretica Linn Ethanolic Extract on Isolated Rabbit Intestine. Technol. Innov. Pharm. Res2021. 9: p. 23-36.

15. Ahmed, A., et al., The pharmacological effects of Fagonia Cretica Linn ethanolic extract on isolated rabbit intestine. Int. J. Pharmacol. Toxicol2013. 1: p. 91-98.

16. Sajid, B., et al., Phytochemical screening and antimicrobial activity of Fagonia cretica plant extracts against selected microbes. Journal of Pharmacy Research, 2011.

17. Jahala¹, O.A.M., et al., In vivo hyperglycemic effect of Fagonia Cretica Linn ethanolic extracts on albino rats. 2014. 3(5): p. 21-23.

18. Kamran, S.H., et al., Antidiabetic and renoprotective effect of Fagonia cretica L. methanolic extract and Citrus paradise Macfad. juice in alloxan induced diabetic rabbits. Journal of Pharmacy &Pharmacognosy Research2017. 5(6): p. 365-380.

19. Nazir, I., et al., Antidiabetic activities of an LC/MS fingerprinted aqueous extract of Fagonia cretica L. in preclinical models. Planta medica2017. 83(14/15): p. 1141-1148.

20. Rawal, A., et al., Rubia cordifolia, Fagonia Cretica Linn and Tinospora cordifolia exert anti-inflammatory properties by modulating platelet aggregation and VEGF, COX-2 and VCAM gene expressions in rat hippocampal slices subjected to ischemic reperfusion injury. Int J Appl Res Nat Prod, 2009. 2(1): p. 19-26.

21. Asif Saeed, M. and A. Wahid Sabir, Effects of Fagonia cretica L. constituents on various haematological parameters in rabbits. J Ethnopharmacol, 2003. 85(2-3): p. 195-200.

22. Abirami, V., et al., Investigation on fagonia cretica -its effect on hormonal profile and immunomodulation in rats. Anc Sci Life, 1996. 15(4): p. 259-63.

23. Lam, M., A.R. Carmichael, and H.R. Griffiths, An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression. PLoS One, 2012. 7(6): p. e40152.

24. Hussain, A., M. Zia, and B. Mirza, Cytotoxic and antitumor potential of Fagonia cretica L. Turkish journal of biology2007. 31(1): p. 19-24.

25. SAEED, M., Z.-U.-D. KHAN, and A.J.T.J.o.B. Sabir, Effects of Fagonia cretica L. Constituents on VariousEndocrinological Parameters in Rabbits. 1999. 23(2): p. 187-198.

26. Zia, K., et al., Anti-bacterial activity and qualitative phytochemical screening of fagonia cretica l. 2016. 59(1): p. 24.

27. Kamran, S., et al., Metabolic Profiling and Investigation of the Modulatory Effect of Fagonia cretica L. Aerial Parts on Hepatic CYP3A4 and UGT2B7 Enzymes in Streptozotocin—Induced Diabetic Model. Antioxidants2023. 12(1): p. 119.

28. Sajid, B., et al., Phytochemical screening and antimicrobial activity of Fagonia cretica plant extracts against selected microbes. 2011. 4(4): p. 962-963.

29. Al-Ziaydi, A.G.T., Protective Effect of Fagonia Arabica (L.) against Alloxan Monohydrate-Induced Diabetes in Albino Wistar Rats. 2015, Doctoral dissertation, Kerbala University.

30. Aboelhassan, D.M., et al., Effect of ethanolic extract of Fagonia cretica on BPA-induced genotoxicity and histopathology in brain and testis tissues of rats. Egyptian Journal of Chemistry, 2022. 65(10): p. 383-396.

31. Yousaf, A., et al., Intrinsic bio-enhancer entities of Fagonia cretica for synthesis of silver nanoparticles involves anti-urease, anti-oxidant and anti-tyosinase activity. Advances in BioscienceBiotechnology2019. 10(12): p. 455-468.

32. RAJANI, V., et al., Potential health benefits and pharmacological activities of fagonia cretica. International Journal Of Advanced Research In Medical & Pharmaceutical Sciences

33. Akhtar, M.F., A. Saleem, and M. Saleem, A comprehensive review on ethnomedicinal, pharmacological and phytochemical basis of anticancer medicinal plants of Pakistan. Current cancer drug targets2019. 19(2): p. 120-151.

34. Aboelhassan, D.M., et al., Effect of ethanolic extract of Fagonia cretica on BPA-induced genotoxicity and histopathology in brain and testis tissues of rats. Egyptian Journal of Chemistry2022. 65(10): p. 383-396.

35. Shah, S.M.A., et al., Nanobiomedicine: A new approach of medicinal plants and their therapeutic modalities. J. Mater. Environ2021. 12(1).

36. Zheng, Y., et al., The combination of nanotechnology and traditional Chinese medicine (TCM) inspires the modernization of TCM: review on nanotechnology in TCM-based drug delivery systems. 2022: p. 1-20.

37. Kumar, R., Nanotechnology in herbal medicine: Challenges and future perspectives, in Nanotechnology in Herbal Medicine. 2023, Elsevier. p. 515-548.

38. Khan, H.A., et al., In-depth in-vitro and in-vivo anti-diabetic evaluations of Fagonia cretica mediated biosynthesized selenium nanoparticles. BiomedicinePharmacotherapy, 2023. 164: p. 114872.

39. Yousaf, A., et al., Intrinsic bio-enhancer entities of Fagonia cretica for synthesis of silver nanoparticles involves anti-urease, anti-oxidant and anti-tyosinase activity. Advances in BioscienceBiotechnology2019. 10(12): p. 455-468.

40. Adnan, M., et al., Research Article Phyto-Extract-Mediated Synthesis of Silver Nanoparticles (AgNPs) and Their Biological Activities. BioMed Research Internationa, 2022.

41. Faisal, S., et al., Fagonia cretica-mediated synthesis of manganese oxide (MnO2) nanomaterials their characterization and evaluation of their bio-catalytic and enzyme inhibition potential for maintaining flavor and texture in apples. Catalysts, 2022. 12(5): p. 558.

42. Zulfiqar, H., et al., Synthesis of silver nanoparticles using Fagonia cretica and their antimicrobial activities. Nanoscale advances, 2019. 1(5): p. 1707-1713.

43. Hussain, R., et al., Casting zinc oxide nanoparticles using Fagonia blend microbial arrest. Applied biochemistrybiotechnology2023. 195(1): p. 264-282.

44. Boateng, J. and O. Catanzano, Silver and silver nanoparticle‐based antimicrobial dressings. Therapeutic dressingswound healing applications2020: p. 157-184.

45. Monteiro, D.R., et al., Silver distribution and release from an antimicrobial denture base resin containing silver colloidal nanoparticles. Journal of Prosthodontics: Implant, EstheticReconstructive Dentistry2012. 21(1): p. 7-15.

46. Bibi, N., et al., Antibacterial efficacy of silver nanoparticles prepared using Fagonia cretica L. leaf extract. InorganicNano-Metal Chemistry, 2019. 49(8): p. 260-266.

47. Hadrup, N., G.J.J.o.T.E.i.M. Ravn-Haren, and Biology, Toxicity of repeated oral intake of organic selenium, inorganic selenium, and selenium nanoparticles: A review. 2023: p. 127235.

48. Dutt, Y., Pandey, R. P., Dutt, M., Gupta, A., Vibhuti, A., Raj, V. S., ... & Priyadarshini, A. (2023). Silver nanoparticles phytofabricated through Azadirachta indica: anticancer, apoptotic, and wound-healing properties. Antibiotics, 12(1), 121.

49. Patil, S. S., Nitalikar, M. M., Das, K., Mallikarjuna, B. P., Alshehri, S., Khormi, A. M. S., ... & Asdaq, S. M. B. (2024). Development of topical silver nano gel formulation of Bixin: Characterization, and evaluation of anticancer activity. Saudi Pharmaceutical Journal, 102125.

50. Nayak, V., et al., Potentialities of selenium nanoparticles in biomedical science. New Journal of Chemistry2021. 45(6): p. 2849-2878.

51. Khan, H.A., et al., In-depth in-vitro and in-vivo anti-diabetic evaluations of Fagonia cretica mediated biosynthesized selenium nanoparticles. BiomedicinePharmacotherapy2023. 164: p. 114872.

52. Shadmehri, A. A., Namvar, F., Miri, H., Yaghmaei, P., & Moghaddam, M. N. (2019). Assessment of antioxidant and antibacterial activities of Zinc Oxide nanoparticles, Graphene and Graphene decorated by Zinc Oxide nanoparticles. International Journal of Nano Dimension, 10(4), 350-358.

53. Mendes, C. R., Dilarri, G., Forsan, C. F., Sapata, V. D. M. R., Lopes, P. R. M., de Moraes, P. B., ... & Bidoia, E. D. (2022). Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens. Scientific reports, 12(1), 2658.

54. Mohd Yusof, H., Abdul Rahman, N. A., Mohamad, R., Hasanah Zaidan, U., & Samsudin, A. A. (2021). Antibacterial potential of biosynthesized zinc oxide nanoparticles against poultry-associated foodborne pathogens: an in vitro study. Animals, 11(7), 2093.

55. Mohd Yusof, H., Abdul Rahman, N. A., Mohamad, R., Hasanah Zaidan, U., & Samsudin, A. A. (2021). Antibacterial potential of biosynthesized zinc oxide nanoparticles against poultry-associated foodborne pathogens: an in vitro study. Animals, 11(7), 2093.

56. Hashim, M.S., et al., Investigation of the antibacterial activity of silver and zinc-containing solutions and Ag: ZnO films against some pathogenic bacteria. Jordan Journal of Biological Sciences2019. 12(4): p. 415-419.

57. Hussain, R., Zafar, A., Hasan, M., Tariq, T., Saif, M. S., Waqas, M., ... & Shu, X. (2023). Casting zinc oxide nanoparticles using Fagonia blend microbial arrest. Applied biochemistry and biotechnology, 195(1), 264-282.

58. Mendes, C. R., Dilarri, G., Forsan, C. F., Sapata, V. D. M. R., Lopes, P. R. M., de Moraes, P. B., ... & Bidoia, E. D. (2022). Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens. Scientific reports, 12(1), 2658.

59. Aggarwal, B.B.; Prasad, S.; Reuter, S.; Kannappan, R.; Yadev, V.R.; Park, B.; Kim, J.H.; Gupta, S.C.; Phromnoi, K.; Sundaram, C.; et al. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases:“reverse pharmacology” and “bedside to bench” approach. Curr. Drug Targets 2011, 12, 1595–1653.

60. Anil, P.; Nikhil, B.; Manoj, G.; Prakash, N. Phytochemicals and biological activities of Fagonia indica. Int. Res. J. Pharm. 2012, 3, 56–59

61. Shehab, N.G.; Mahdy, A.; Khan, S.; Noureddin, S. Chemical constituents and biological activities of Fagonia indica Burm F. Res. J. Med. Plant 2011, 201, 1.

62. Rashid, U.; Khan, M.R.; Jan, S.; Bokhari, J.; Shah, N.A. Assessment of phytochemicals, antimicrobial and cytotoxic activities of extract and fractions from Fagonia olivieri (Zygophyllaceae). BMC Complement. Altern. Med. 2013, 13, 1–7.

63. Zhang, H.; Hao, F.; Yao, Z.; Zhu, J.; Jing, X.; Wang, X. Efficient extraction of flavonoids from Polygonatum sibiricum using a deep eutectic solvent as a green extraction solvent. Microchem. J. 2022, 175, 107168

64. Zainal-Abidin, M.H.; Hayyan, M.; Hayyan, A.; Jayakumar, N.S. New horizons in the extraction of bioactive compounds using deep eutectic solvents: A review. Anal. Chim. Acta 2017, 979, 1–23.

65. Rodríguez De Luna, S.L.; Ramírez-Garza, R.; Serna Saldívar, S.O. Environmentally friendly methods for flavonoid extraction from plant material: Impact of their operating conditions on yield and antioxidant properties. Sci. World J. 2020, 2020, 6792069.

66. Sagandykova, G.N.; Pomastowski, P.P.; Buszewski, B. Multi-instrumental approach to unravel molecular mechanisms of natural bioactive compounds: Case studies for flavonoids. TrAC Trends Anal. Chem. 2020, 126, 115865.

67. Lanjekar, K.J.; Rathod, V.K. Green extraction of Glycyrrhizic acid from Glycyrrhiza glabra using choline chloride based natural deep eutectic solvents (NADESs). Process Biochem. 2021, 102, 22–32

68. Doldolova, K.; Bener, M.; Lalikoğlu, M.; Aşçı, Y.S.; Arat, R.; Apak, R. Optimization and modeling of microwave-assisted extraction of curcumin and antioxidant compounds from turmeric by using natural deep eutectic solvents. Food Chem. 2021, 353, 129337.

69. Wang, G.; Cui, Q.; Yin, L.-J.; Zheng, X.; Gao, M.-Z.; Meng, Y.; Wang, W. Efficient extraction of flavonoids from Flos Sophorae Immaturus by tailored and sustainable deep eutectic solvent as green extraction media. J. Pharm. Biomed. Anal. 2019, 170, 285–294

70. Wang, J.-R.; Li, Y.-L.; Zhang, H.-T.; Xiang, Z.-B.; Zuo, J.; Peng, B.; Liu, X.-Y.; Ou, H. Ultrasound-assisted extraction of flavonoids from Rudbeckia hirta L. flowers using deep eutectic solvents: Optimization, HPLC analysis and anti-inflammatory activity. J. Appl. Res. Med. Aromat. Plants 2024, 45, 100618.

71. Ijardar, S.P.; Singh, V.; Gardas, R.L. Revisiting the physicochemical properties and applications of deep eutectic solvents. Molecules 2022, 27, 1368

72. Hansen, B.B.; Spittle, S.; Chen, B.; Poe, D.; Zhang, Y.; Klein, J.M.; Horton, A.; Adhikari, L.; Zelovich, T.; Doherty, B.W. Deep eutectic solvents: A review of fundamentals and applications. Chem. Rev. 2020, 121, 1232–1285

73. Mjalli, F.S. Mass connectivity index-based density prediction of deep eutectic solvents. Fluid Phase Equilibria 2016, 409, 312–317

74. Ghatee, M.H.; Bahrami, M.; Khanjari, N. Measurement and study of density, surface tension, and viscosity of quaternary ammonium-based ionic liquids ([N222 (n)] Tf2N). J. Chem. Thermodyn. 2013, 65, 42–52.

75. Li, C.; Zhang, J.; Li, Z.; Yin, J.; Cui, Y.; Liu, Y.; Yang, G. Extraction desulfurization of fuels with ‘metal ions’ based deep eutectic solvents (MDESs). Green Chem. 2016, 18, 3789–3795.

76. Khan J, Asaf S, Lubna, Abdelbacki AM, Jan R, Kim KM. Green Extraction of Antioxidant-Rich Flavonoids from Fagonia cretica Using Deep Eutectic Solvents. Molecules. 2025 Feb 10;30(4):813.

77. Fernández-Estellé, M.; Hernández-González, V.; Saurina, J.; Núñez, O.; Sentellas, S. Characterization and classification of Spanish honeydew and blossom honeys based on their antioxidant capacity. Antioxidants 2023, 12, 495

78. Gao, C.; Cai, C.; Liu, J.; Wang, Y.; Chen, Y.; Wang, L.; Tan, Z. Extraction and preliminary purification of polysaccharides from Camellia oleifera Abel. seed cake using a thermoseparating aqueous two-phase system based on EOPO copolymer and deep eutectic solvents. Food Chem. 2020, 313, 126164

79. Patel J, Kalsariya B. A Comparative Standard Manufacturing procedure of Swarjika Kshara prepared from Ushtrapriya (Fagonia cretica Linn.) and Rudanti (Cressa cretica Linn.). International Journal of Ayurveda and Pharma Research. 2025 Mar 7:1-9.

80. Sadananda S. Rasa Tarangini, Edited by Kashinath Shastri. New Delhi: Motilal Banarasidas publication. 1979:39-40.

81. Husain MK, Pratap GP, Alam M, Javed G, Minhajuddin A, Khan AA. Traditional uses and properties of Indian medicinal plants in the treatment of vitiligo. InMedicinal and Aromatic Plants of India Vol. 2 2023 Nov 1 (pp. 191-212). Cham: Springer International Publishing.

82. Sheikh FA, Naz IQ, RAHMAN L, YOUNIS T, SHINWARI ZK, FAISAL R. Genus Fagonia mediated nanoparticles and their therapeutic potential: a review. Pak. J. Bot. 2024;56(4):1623-9.

83. Iftikhar N, Chatha SA, Ahmad T, Ali Q, Hussain AI, Rathore HA. Fagonia arabica L.: a review of its phytochemistry, pharmacology and traditional uses. Combinatorial Chemistry & High Throughput Screening. 2022 Jul 1;25(7):1187-99.

84. Puri D, Bhandari A. Fagonia: a potential medicinal desert plant. Journal of Nepal Pharmaceutical Association. 2014;27(1):28-33.

85. SAEED M, KHAN ZU, Sabir AW. Effects of Fagonia cretica L. Constituents on VariousEndocrinological Parameters in Rabbits. Turkish Journal of Biology. 1999;23(2):187-98.

86. Kashif M, Abbas A, Nasir A, Rehman AU, Rehman E, Jamal MA, Kazi M. Exploring the Antiproliferative and Antioxidant Effects of Fagonia cretica Thereof: An In Vitro and In Vivo Evaluation. Microscopy Research and Technique. 2025 Feb 24.

Phytochemical, Pharmacological, Toxicological, and Nanotechnology Based Materialistic Approach of Fagonia Cretica Linn.

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