Chemical Insights and Therapeutics Potential of Fagonia Arabica in Modern Medicines

Abstract

Plants are itself a chemical laboratory which synthesize a million of compounds per second Throughout their life span, some of them are essential for their life cycle and remaining are stored as the secondary metabolites like alkaloids, glycoside, flavonoids, resins etc… for the various secondary functions. This review elaborates various biological compounds, their chemical characterization and pharmacological characterizations and their correlational responses with the specific chemical compounds. Fagonia arabica is one of the most potent and effective herbal remedies on the various disease and disorders it possess many traditional claims for the actions like sore mouth and small pox, haematological, neurological, endocrinological, dermatological and inflammatory disorders, small pox and endothermic reactions in the body jaundice, fever abscesses blood purification, fever, cold, cough astringent, febrifuge, small pox, fever, thirst, vomiting, dysentery, asthma, urinary discharges, liver trouble, typhoid, toothache, stomach troubles and skin diseases, anti-tumor. That’s why we have area of interest on the fagonia arabica to evaluate the chemical compounds or their secondary metabolites in concerned to their pharmacological actions and to find the future perspective in modern treatment and how it plays the functional role to potentiate health.

Keywords

Introduction

Medicinal plants are a natural gift to humanity, aiding in the pursuit of a healthful, disease-free life. Globally, there exists a rich cultural understanding of herbal medicine, with two-thirds of newly identified chemicals each year derived from higher plants. Herbal remedies are particularly significant in healthcare initiatives, especially in developing nations, as they often present a safer alternative to modern synthetic medications, exhibiting minimal or no side effects. Typically, herbal formulations utilize either fresh or dried parts of plants. The use of medicinal plants is prevalent among indigenous populations in rural areas of many developing countries. Fagonia Arabica is one such medicinal plant known for its ability to treat a variety of ailments. This species belongs to the Zygophyllaceae family, recognized for its medicinal significance. F. arabica is a tropical herb found throughout the Indian subcontinent and is commonly referred to by names such as Dhamasa, Suchi boti, dhamanian kunda, Damoo, Shaukat-e-Albeefa, and Shokat-e-albaiza. It typically grows to a height of 1 to 3 feet and thrives on calcareous rocks, primarily in regions of Africa, Afghanistan, India, and Pakistan. The genus Fagonia is found in sandy plains, calcareous coastal ridges, and desert wadis, with notable occurrences in Gujarat and Tamil Nadu within India. Fagonia species have been extensively researched for their antitumor, antioxidant, analgesic, astringent, febrifuge properties, and their potential as prophylactics against smallpox. Traditionally, they are utilized for treating conditions such as cancer, fever, asthma, toothaches, urinary disorders, gastrointestinal issues, and kidney ailments. The plant is also beneficial for skin diseases, wound healing, smallpox, vertigo, foul odors, abscesses, scabies, infected ulcers, and scrofulous gland wounds, as well as for various dermatoses. Additionally, it possesses antiviral, antimicrobial, antiseptic, and anti-inflammatory properties, and has applications in liver cancer treatment and thrombolytic action. Fagonia Arabica is recognized for its blood-purifying abilities and acts as a deobstruent. The twigs of this plant are also employed as a remedy for snake bites.

The plant is known to produce diterpenes, including fagonone and its derivatives, as well as flavonoids. Additionally, triterpenoid and sterol glycosides have been identified within the plant. The leaves are rich in flavonoids such as quercetin and kaempferol, while the fruits are a source of ascorbic acid. Historically, various plants have provided straightforward remedies for human ailments, with different spices being associated with the treatment of specific diseases. The World Health Organization (WHO) recognizes that a significant portion of the global population, approximately 80 percent, relies on traditional remedies for essential healthcare services. However, many plants utilized for diverse health issues have not undergone thorough scientific investigation. In Ayurveda, the traditional Indian healthcare system, numerous herbal formulations are employed as neuroprotective agents. For a long time, these formulations have been utilized to address various health concerns, including hematological and hepatic disorders, as well as inflammatory conditions. Fagonia arabica, commonly referred to as ‘Dhamasa,’ is a tropical herb from the Zygophyllaceae family, prevalent throughout the Indian subcontinent. This green shrub typically grows to a height of 1 to 3 feet and is found on calcareous rocks across the Mediterranean regions of Africa, Afghanistan, India, and Pakistan. Various parts of this herb have been traditionally used to treat a range of ailments, including hematological, neurological, endocrinological, and inflammatory disorders. It is also noted for its rich content of antioxidants and triterpenoid saponins. The infusion of this plant serves as an effective cooling agent for stomatitis, purifies the blood, and acts as a deobstruent. Furthermore, it is utilized in the treatment of skin diseases, smallpox, and for managing endothermic reactions in the body. The twigs are employed as a remedy for snake bites and are also applied externally as a paste for tumors and swelling in the neck.

1. 1. HISTOLOGICAL ACCOUNT: The plant is known to contain diterpenes, including fagonone and its derivatives, as well as flavonoids. Additionally, triterpenoid and sterol glycosides have been identified within the species. The earliest recorded mention of Fagonia herb does not originate from a medicinal authority but rather from the seventh-century Arabic poet Amro Ibn Al Ahmer. This octogenarian poet wrote a poem while suffering from terminal ascites, in which he described drinking Al Shokaa (the Arabic name for Fagonia) and chewing it under his tongue as a means of seeking recovery. Ayurveda also references its use in various forms long before the current era. In the modern period, Carl Linnaeus established the genus Fagonia in his work Species Plantarum in 1753, initially recognizing three species. Today, the genus comprises 35 species. The name Fagonia honors G.C. Fagon, a Professor of Botany and Director of the Jardin de Roi in Paris. Significant contributions to the phylogeny and taxonomy of the Fagonia genus have been made by Beier and colleagues, starting with morphological characteristics and extending to molecular details, which have further informed the understanding of the plants' biogeography through parsimony and Bayesian model averaging.
   2. OCCURANCE: The genus Fagonia is restricted to warm and arid regions across all continents, with the exception of Australia. This genus includes shrubs, shrublets, or herbs, each displaying unique characteristics. Fagonia belongs to the family Zygophyllaceae. The plants typically range in height from 20 to 55 cm, and their coloration can vary from dark to pale green, depending on the species. Additionally, species within the Fagonia genus show various morphological distinctions.
   3. TAXONOMICAL CLASSIFICATION:

Botanical Name- Fagonia arabica

Kingdom- Plantae

Phylum- Tracheophyta

Class -Magnoliopsida

Order - Zygophyllales

Family- Zygophyllaceae

Subfamily- Zygophylloideae

Genus- Fagonia

Species – arabica

Common name :- Dhamasa

Synonyms :- Brevispina Maire

1.4 MORPHOLOGY : Fagonia arabica is a small, spiny, upright undershrub that exhibits a degree of glandularity. Its branches are slender, cylindrical, and smooth, with a triate appearance. Morphological analysis indicates that the stem has a whitish-green hue, with internodes measuring between 1.6 to 3 cm in length. The stem is cylindrical and possesses a distinctive odor, accompanied by a taste that is sweet, bitter, sharp, and sour, with a short fracture. The surface is adorned with minute hairs. Fagonia arabica belongs to the genus Fagonia, which comprises wild flowering plants native to warm, arid regions across Africa, the Mediterranean, the Middle East, and India. Commonly referred to as Virgin's Mantle in English, Fagonie in German, and Shawka al-Baidaa in Arabic, this plant has several notable characteristics:

1. Size: A green shrub that typically reaches heights of 1 to 3 feet.

2. Leaves: Thin, spine-like leaves featuring two or more thorns.

3. Flowers: Pink or purple flowers measuring 8 to 10 millimeters in width and 6 millimeters       in length.

4. Stems: Upright stems.

5. Stipules: Free, pointed, or spine-like stipules.

6. Capsule: An obconical, hairy capsule that is loculi-cidal.

1.5 MICROSCOPIC CHARACTER : The transverse section of the stem exhibits an irregular circular shape. The epidermis is formed by a single layer of rectangular cells, which is covered by a thin cuticle layer that contains a few stomata. The cortex comprises multiple layers of collenchymatous and parenchymatous cells. Within the cortex, one can find lignified sclerenchyma fibers, mucilaginous brownish substances, and sclereids, which may be present individually or in clusters. The stellar region is made up of xylem, phloem, and medullary rays. The xylem appears as wedge-shaped patches, separated by multiseriate medullary rays, and consists of numerous lignified pitted xylem vessels along with xylem parenchyma. The phloem is structured like caps over the metaxylem. Medullary rays resemble the spokes of a wheel and are composed of thin-walled elongated parenchymatous cells filled with starch grains. The pith, located at the center of the stem, consists of large parenchymatous cells that may be lignified or unlignified, along with abundant brownish matter, lignified sclerenchymatous fibers, fragments of quadrangular-shaped epidermis, anomocytic stomata, and remnants of lignified pitted and spiral vessels. Irregular, lignified, stratified sclereids are found either singly or in bands with varying lumen sizes, and minute simple starch grains can be observed under a microscope.

2.METHODS : In the present study, Fagonia arabica was utilized. Phytochemicals were extracted employing four distinct solvents: ethanol, methanol, chloroform, and water. The concentrations of total phenolics, photosynthetic pigments, and carotenoids were determined.

2.1 PHYTOCHEMICAL SCREENING :

Numerous bioactive compounds, such as glycosides, flavonoids, terpenoids, saponins, alkaloids, and trace elements, have been identified in the Fagonia arabica plant. Additionally, the isolation and characterization of two flavonoid glycosides, namely kaempferol-7-O-rhamnoside and acacetin-7-O-rhamnoside, have been documented. An early study from 1977 highlighted 8-O-methylherbacetin-3-rutinoside as the predominant component of Fagonia arabica. Furthermore, significant research into the phytochemistry of Fagonia arabica revealed for the first time that kaempferol and isorhamnetin-3-rutinosides are the primary flavonoids present in F. mollis, while F. tristis also contains 8-O-methylherbacetin. This study involved a preliminary phytochemical screening of the sequential extracts of F. arabica to explore a range of secondary metabolites.

1. 1. 1. ESTIMATION OF TOTAL PHENOLS AND FLAVONOIDS CONTENT:

Spectrophotometry was employed to assess the total phenolic content in the plant extract, as documented in prior studies. Calibration curves for gallic acid (GA) were established within the range of 20–100 ng/mL. The phenolic content of the extract was then standardized to gallic acid equivalents (GAEs), reported as mg GAE/g of dry weight (dw). The overall concentration of phenols was determined using the calibration curve represented by the equation (y = 0.001x + 0.113).

To evaluate the total flavonoid concentration, a colorimetric assay utilizing the aluminum chloride method was conducted. Standards for quercetin concentrations were prepared, ranging from 20 to 100 µg/mL. For the measurement of quercetin concentrations in methanol, 1 mL of each quercetin standard was added to a 10 mL volumetric flask containing 4 mL of double-distilled water. At time t = 0, three reagents were introduced: 0.3 mL of 5% sodium nitrite, 0.3 mL of 10% aluminum chloride, and 2 mL of 1M sodium hydroxide. Following the rapid addition of 2.4 mL of double-distilled water, the solution was prepared for analysis. The absorbance of the resulting pink mixture was measured at 510 nm against a blank sample devoid of quercetin. The calibration curve was generated based on the standard absorbance values of quercetin. Flavonoid concentrations were expressed in quercetin equivalents (y = 0.265 × 0.152) as mg QE/g of dry weight.

2.1.2:  GCMS ANALYSIS

As previously mentioned, a GC-MS analysis was performed on various solvent extracts of F. arabica. This analysis utilized a GC-MS instrument (model GCMS-QP2010S) that featured a fused silica column. Helium served as the carrier gas, maintained at a steady flow rate of 1 mL/min to facilitate separation. A volume of 1 μL of the methanol extract from F. arabica was introduced into the system via a split injector. The column temperature was initially set to 80 °C, while the injector temperature was adjusted to 260 °C. During the analysis, the temperature was programmed to increase at a rate of 10 °C per minute, with the following parameters: column flow at 1.00 mL/min, pressure at 65.0 kPa, linear velocity at 36.8 cm/s, total flow at 24.0 mL/min, and purge flow at 3.0 mL/min. The identification of the primary components of the plant extract was confirmed by comparing the relative retention times and mass spectra with those of standard compounds.

1. 1. 3. Liquid Chromatography–Mass Spectrometry (LC-MS) ANALYSIS

We conducted an analysis of the chemical constituents in a methanol fraction of F. arabica using a binary pump in conjunction with an LC-MS-8040 system from Shimadzu. The mass spectrometer, equipped with Electrospray Ionization (ESI), was integrated with the high-performance liquid chromatography (HPLC) setup. For this analysis, a C18 HPLC column was employed. The solvent flow rate was set at 0.2 mL/min, utilizing a methanol-to-water ratio of 80:20. Detection was performed in direct injection mode with a positively charged ESI probe. The sample was delivered at a flow rate of 8 μL/min, and the capillary temperature was kept at 280 °C. A total of 3 μL of the sample was injected for the analysis.

Phytochemical analysis of different solvent extracts of F. arabica.

 “+” means “present”; “−” means “absent”.                                              

1. 2. PHARMACOLOGICAL SCREENING :

2.2.1 MEDICINAL USES : The Fagonia arabica plant is recognized for its extensive traditional applications, particularly in anti-inflammatory, analgesic, antipyretic, and antioxidant functions. Various bioactive compounds, such as glycosides, flavonoids, terpenoids, saponins, alkaloids, and trace elements, have been identified in this plant. It is beneficial for treating skin conditions, promoting wound healing, addressing smallpox, alleviating vertigo, managing foul abscesses, scabies, infected ulcers, and scrofulous gland wounds, as well as for various dermatoses. Additionally, it is utilized for its antiviral, antimicrobial, and antiseptic properties, and is also indicated in cases of liver cancer and thrombolytic action. Furthermore, it is known to purify the blood and serves as a deobstruent.

PHARMACOLOGICAL ACTIVITY :

Antioxidant Activity

Certain researchers have indicated that the phenolic compounds found in the plant exhibit antioxidant properties. Additionally, another study highlighted the plant's analgesic, anti-inflammatory, and antipyretic effects, which were previously identified alongside its antioxidant activity, thereby elucidating the mechanism of action. The plant contributes to the restoration of antioxidant enzymes and reduces lipid peroxidation.

Thrombolytic Activity

The thrombolytic properties of Fagonia arabica were evaluated in vitro using a clot lysis model, demonstrating a 75.6% reduction in clot formation, suggesting its potential as a therapeutic option for patients with atherothrombotic conditions. Additionally, another study investigated the effects of Fagonia arabica in conjunction with fish extract from Heteropneustes fossilis, revealing superior outcomes compared to the plant extract used alone. Furthermore, a researcher reported the thrombolytic activity of this plant through the induction of thrombin, which activates tissue plasminogen activator (t-PA) and inhibits plasminogen activator inhibitor-1 (PAI-1), with experiments conducted on human umbilical cord cells.

Antimicrobial

The methanolic extract of Fagonia arabica demonstrates efficacy against both Gram-positive and Gram-negative bacteria, as well as Candida albicans. The size of the inhibition zone produced by the F. arabica extract varied depending on the bacterial species tested. Escherichia coli exhibited the strongest inhibitory effect, measuring 28 mm, followed by Streptococcus pyogenes, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Conversely, Proteus vulgaris showed no inhibitory effect. Fagonia arabica is recognized for its antibacterial properties, particularly against the two strains, Escherichia coli and Staphylococcus aureus.

Antidiabetic

An ethanolic extract derived from Fagonia arabica demonstrated a reduction in blood glucose levels in a diabetic rat model. This plant exhibits significant antidiabetic properties, likely attributed to its abundant phytochemical composition. Its capacity to lower blood glucose, maintain body weight, boost insulin secretion, and increase glycogen levels positions it as a promising subject for further research and potential therapeutic applications in the management of diabetes.

Antioxidant

Fagonia arabica has the ability to support the maintenance of cellular ATP and lactic acid levels, which may avert cell death resulting from ischemia/reperfusion. Its antioxidant properties contribute to the reduction of oxidative stress caused by ischemia-reperfusion, enabling cells to sustain their ATP and lactic acid levels, thereby ultimately preventing cell death associated with ischemia/reperfusion.

Anti-inflammatory and Wound healing property.

Contraindications exist for the use of calcified diclofenac sodium solution (Diclomax ®) and povidone-iodine (Betadine) in wound care. Topical application of natural gels and diclofenac sodium oil (0.5 g) on the surface of the left hand claw resulted in a calming effect within three hours. The use of 0.5 g of F. arabica gel demonstrated positive corrective effects on wounds. Betadine was administered every 19 days to individuals with yellow skin and was utilized for treating rat extraction injuries over a four-day duration. It is evident that there is a need to mitigate the reformist influence on prison definitions and to promote faster wound healing. The plant could serve as a preventive measure to reduce various gel formulations and facilitate wound recovery.

Androgenically active.

Fagonia concentrates on arabica in F. Alcoholic, examining the aerial components of the Creticon estrus cycle and the implications of implantation in female yellow-skinned rats. Upon investigation, it became evident that Fagonia was encountering criticism. The stability of the estrus pattern in rats exhibited an arbitrary overshoot during the warm period (estrus phase). Its unseen index stands at +53.33, which diminishes the inclination to coexist with females. When administered at a dosage of 250 mg/kg orally, the results shifted entirely against the implantation specialist. The suspension drug shows a significant androgenic effect, characterized by the expansion of both the primary vesicles and the abdominal prostate, in comparison to the control suspension. Symptoms resulting from treatment with testosterone propionate, which possesses antiandrogenic properties, may not necessarily be mitigated when administered in combination with the two.

Counter-Activity.

The ability of Fagonia arabica to strengthen cells in pheochromocytoma (PC12) in rats subjected to synthetic ischemia, along with its role as a cancer prevention agent, has been examined [Satput et al. (2009)]. The variations in cancer prevention proteins, including Turf, Cat, GSHPX, and GH-R, have been assessed. The potential of the anti-cancer agent was evaluated through various metrics, such as ABTS (anti-cancer agent spice potential), the degree of lipid peroxidation (measured by MDA and 4-HAE), total antioxidant status (TAS), and total glutathione levels (including reduction, oxidation, and their ratios). The findings indicated that Fagonia arabica exhibited significant antioxidant activity, reaching a peak of 1000 µg/ml. Treatment of ischemic cells with this extract resulted in an increase in GSH levels, which contributed to the restoration of TAS and a reduction in lipid peroxidation levels. Fagonia arabica effectively neutralizes free radicals and mitigates oxidative stress during ischemic conditions. Further guided tests are planned to evaluate the antioxidant properties and the activity of free radical scavengers associated with plant extracts.

Clotlytic activity.

Do not belittle the outcomes associated with thrombotic diseases, such as myocardial or cerebral complications, in intravenous trapped groups. Thrombolytic specialists are now familiar with a specific group of veins. Utilizing an in vitro thrombolytic technique, the aqueous extract of the entire Fagonia arabica plant demonstrates a significant level of cluster formation, with streptokinase negative control and water negative control showing results of 75.6% in blood and hematology-related assessments.

2.2.2. TRADITIONAL CLAIMS :  

A comprehensive and intriguing compilation of diseases and disorders is presented, which are believed to be treatable with Fagonia arabica. The proposed treatment methods encompass both internal and external applications, tailored to the specific condition being addressed. The ailments listed include, but are not limited to, sore mouth, smallpox, hematological, neurological, endocrinological, dermatological, and inflammatory disorders. Additionally, it addresses conditions such as jaundice, fever, abscesses, blood purification, cold, cough, astringent effects, febrifuge, thirst, vomiting, dysentery, asthma, urinary issues, liver problems, typhoid, toothache, stomach ailments, skin diseases, and anti-tumor properties.

3. CYTOTOXICITY STUDIES :

This study employed an MTT assay to assess the effectiveness of different solvent extracts from F. arabica. It was observed that the viability of the non-cancerous L929 cell line diminished with increasing concentrations of the extracts. At elevated doses, the toxic effects of nearly all the extracts tested were evident. The hexane, ethyl acetate, methanol, and aqueous extracts notably reduced cell viability as their concentrations increased.

4. INDUSTRIAL APPLICATIONS OF FAGONIA ARABICA FOR IMPROVES THE STATUS OF HEALTH:

Fagonia arabica possesses numerous industrial applications, which include the following:

• Nanoparticle synthesis: The extract from the polar leaves of Fagonia arabica can facilitate the production of gold nanoparticles. 

• Pharmaceutical and pharmacological uses: Fagonia arabica exhibits a diverse array of biological activities, such as antioxidant, antimicrobial, cardioprotective, and anticoagulant effects. It has been utilized in the treatment of various conditions, including hematological, neurological, endocrinological, and inflammatory disorders. 

• Thrombolytic properties: Fagonia arabica demonstrates thrombolytic capabilities and may serve as an alternative to conventional thrombolytic medications. 

• Diuretic effects: The dried leaves and stems of Fagonia arabica are known for their diuretic properties. 

• Treatment for skin diseases: Fagonia arabica is employed in the management of skin ailments. 

• Remedy for snake bites: The twigs of the plant are utilized as a treatment for snake bites. 

• Tumor treatment: The twigs can be applied externally as a paste to address tumors. 

• Treatment for neck swellings: The twigs are also used externally as a paste for swellings in the neck. 

CONCLUSION:

It is clear from the review that numerous researchers are exploring various facets of Fagonia arabica. Nevertheless, the quantity of studies conducted and the range of purported therapeutic applications remain imbalanced. There exists significant potential to examine the different parts, fractions, and components of the Fagonia arabica species, as well as to clarify the mechanisms involved. Further research and exploration are essential to fully comprehend this genus for the benefit of humanity.

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