Phytochemistry, Pharmacological Properties and Medicinal Uses of Apium leptophyllum: A Review

Apium leptophyllum seeds are used as an important drug in Ayurveda from ancient times. The main constituents of the seed are fats, fibre, carbohydrates and essential oils, about 50% of which consists of Thymol. Chromatographic analysis of the seed showed various essential compounds viz. Pentacosanol, β-Sitosterol, 1-nonadecanol, 8-hydroxy cuminic acid, Corosolic acid and Stigmasterol. The seeds have shown strong antioxidant properties along with various other pharmacological properties like anti-microbial, anti-fungal, anti-diabetic, anti-inflammatory, anti-diarrheal, anti-asthmatic and anti-cancer properties. This review aims to provide a comprehensive overview of scientific research literature on the chemical composition and pharmacological activities of Apium leptophyllum. We are the first to report vast and updated review of this plant, as much of the work has not been done on this plant. So this review may be helpful for the researchers to explore the pharmacological properties of this plant which may lead to new discoveries in drug development.


INTRODUCTION
There is a rising demand for plant-based medicines, pharmaceuticals, food supplements, health products, cosmetics etc which are derived from plants.From times immemorial, various societies have resorted to nature, mainly to plants as medicine and health sources.Today, a large number of people particularly in under developed and developing countries uses these traditional plants for primary needs of medicinal assistance. [1]As an estimate of the World Health Organization (WHO), about 80% of the world population still uses these herbs and other traditional medicines for their medicinal use.Polysaccharides from medicinal herbs have received a lot of significance in recent decades because of their notable bioactivities, such as anti-proliferative, antioxidant, anticoagulant, radioprotection effect, antiviral activity, hypolipidemic, antidiabetic and immunomodulatory activities, which make them worthy for medicinal uses. [2]Traditional medicines and medicinal herbs are widely used as curative agents in most underdeveloped countries for maintaining of sound health. [3]The antibacterial, antioxidant and antipyretic actions of phytochemicals present in these plants could explain their medicinal properties. [4]o these plants should be investigated to have good comphrension of their qualities, protection, and efficacy. [5]The word "herbal drug" refers to the plant parts (seeds, leaves, flowers, roots, barks, stems, and so on) that are used to make medications.Furthermore, the World Health Organization (WHO) defines medicinal plants as herbal remedies made by subjecting plant materials to extraction, fractionation, purification and concentration and which can be made for utilization or as a base for herbal products.Because information on the usage of plant species has been passed down through oral tradition from one generation to the next, knowledge of therapeutic plants has begun to dwindle.As a result of a shift in socio-economic changes and attitude, knowledge of therapeutic plants has become obsolete. [6]The Ayurveda system in India has detailed a vast number of plant or plant product-based remedies.The exploration of their morphological, pharmacognostical or pharmacological uses can help us understand their active principles and mode of action, which can help in exploring different medicinal plants.
Fir-leafed celery and Marsh parsley are common names for Apium leptophyllum, which belongs to the Apiaceae (Umbelliferae) family.It's called "Ajmoda" in Hindi.The plant is found in North America, but it is present all over the world, from warm tropical to temperate latitudes, and it is known as noxious weed in many places.It's a herb with tap-rooted branching and thread-like green leaves that grows to just over half a metre.Ajamoda (Apium leptophyllum) was discovered in Pakistan, South America, Sri Lanka, Queensland, India and the tropics. [7]he Umbelliferous fruit 'Apium leptophyllum' is an essential drug in the Siddha, Ayur-veda, and Unani systems of medicine.Fruits of Apium leptophyllum are used in the drug formulations.Ajmoda is an annual plant that can reach a height of 2 feet.It thrives on soils that are acidic, neutral, or basic (alkaline).Cooked leaves are consumed, while the plant's seeds are utilized as a condiment.The plant's seeds are tiny and yellowish brown and have a pleasant scent and a slightly bitter-pungent flavour.

Muell ex Benth
Color -Light brown to yellow Shape-Oval and spherical to spherical and mericarps are not curved Size -2mm length and about 2mm in width Surface-Glabrous to naked eye and ridges straight

Microscopic Characters
Microscopy is required for the observation of adulterants and defilement in herbal production, as well as for determining the validity and quality of herbal remedies.During microscopic study of crude pharmaceuticals, the shape, size, and relative position of distinct cells and tissues, as well as the chemical nature of cell walls and the form and nature of cell contents, are all taken into account.
Saraswathya and other coworkers in 2013 demonstrated the microscopic characters of Apium leptophyllum.They have reported that the epidermal cells are straight walled; they are generally 80 microns long, 50 microns broad and papillae present.The vascular system's patchy extensions with pitted sclerenchymatous cells are present in the mesocarp, but there is no full mesocarpic sclerenchymatous layer.Parquetry arrangement is not found in endocarp.A vascular bundle of spiral, tracheids, and reticulate vessels and sclerenchyma cells with oblong pits supports the ridges; thin xylem fibres are also present.The seed is endospermous, a single layer called testa is on the posterior side, but it is present with some more tissue layers on the commissural side, embryo is embedded in the endosperm; cell walls of the endosperm uniformly thick, cells packed with aluerone grains. [17]These studies will be helpful in the identification of Apium leptophyllum for researchers who want to work on this plant.

Chemical Composition and Isolated Compounds
Chemical composition of Apium leptophyllum is given in Table 1 and isolated compounds from Apium leptophyllum and their structures are given in

Antioxidant Properties
Oxidative stress and an increase in free radical levels are two of the most important core markers linked to a variety of progressive pathological illnesses, including neurological disorders, cancer, ageing, and endocrine disease. [25]Many chronic health disorders are caused by free radicals and antioxidants can help us by preventing free radical formation.New sources of antioxidants of natural origin that are both economically viable and safe are being researched.Medicinal plants as natural antioxidants have gained in popularity as a therapeutic choice.Natural antioxidants found in medicinal plants include flavonoids, Vitamin C, tocopherol, and other phenolic substances. [26]Secondary metabolites protect living organisms against harm caused by unrestricted formation of reactive oxygen species (ROS), DNA strand breaking, protein damage, and concurrent lipid peroxidation. [27]Because of the presence of various important active chemicals such as phenol, tannins, flavonoid, coumarins, and terpenoids, medicinal plants are currently found to have free radical scavenging action. [28]mong the different naturally occurring traditional medicinal plants, Apium leptophyllum has been reported for its strong antioxidant activities of in-vivo and in-vitro studies.When compared to conventional ascorbic acid, Apium leptophyllum seed extracts showed considerable antioxidant activity by reducing hydroxyl, DPPH, nitric oxide and superoxide radicals, which could be owing to the high phenolic and flavonoidal content. [29]Due to its high free radical scavenging activity the essential oil of Apium leptophyllum is used for the curative agent of "Mitch", the inflammatory disease which causes the formation of free radicals.Scavenging of such radicals by the oil is helpful to control the general symptoms of "Mitch" such as inflammation. [10]DPPH radical scavenging activity is being performed to screen the antioxidant potential of plant extracts.The scavenging effect percentage of DPPH on various extracts of Apium leptophyllum with different concentrations was studied by Sahoo and other researchers in 2013.They have found the IC 50 values of methanolic, aqueous, ethanolic extract and Ascorbic acid at 97.9, 123.52, 217.32, 20.98 µg/ml respectively.Thus, they have revealed in their study that the methanol extracts showed higher DPPH radical scavenging activity as compared to other extracts. [11]The radical scavenging activity of the essential oils of Apium leptophyllum on DPPH was also determined spectrophotometerically by Asamenew and other researchers in 2008.They found that adding the volatile oil to the mix decreased DPPH in a concentration dependent manner. [10]The constituents terpinene and terpinene-4-ol, which have been stated in the literature to have strong radical scavenging activity. [30,31]Shukla and other researchers in 2001 also reported concentration dependent free radical scavenging activity of aqueous and ethanolic extracts of Apium leptophyllum by DPPH assay.Through oxidation of essential thiol (-SH) groups Hydrogen peroxide a oxidizing agent that inactivates a few enzymes directly. [32]Various researchers have evaluated the H 2 O 2 scavenging activity of Apium leptophyllum to check the antioxidant property of Apium leptophyllum.They reported a concentration dependent inhibition of H 2 O 2 radical scavenging. [11,19]Methanolic extract have been found to have better hydroxyl radical scavenging ability. [11]Nitric oxide inhibition is another powerful assay to check the antioxidant activity of plant extracts.The works on the principle that sodium nitroprusside in aqueous solution at physiological pH, generates nitric oxide which interacts with oxygen to produce nitrite ions that can be estimated using Griess reagent.Various studies have been conducted to evaluate the nitric oxide scavenging activity of Apium leptophyllum and found inhibition of nitric oxide radicals in a dose dependent manner. [11,19]Sahoo and other researchers in 2013 have also reported superoxide radical scavenging of Apium leptophyllum in a concentration dependent manner.They found that the methanolic extract is more effective than other extracts of Apium leptophyllum. [11]Reducing power assay method works on the principle that substances having reduction potential, react with potassium ferricyanide (Fe 3+ ) to form potassium ferrocyanide (Fe 2+ ), which then reacts with ferric chloride to form ferric-ferrous complex that has an absorption maximum at 700 nm.Presence of the polyphenolic compounds in the plant extracts is responsible for the reducing power capacity. [33]The reducing power of seed extracts of Apium leptophyllum was determined by various researchers to evaluate its antioxidant property; they have reported concentration dependent effect of Apium leptophyllum. [34,19]The antioxidant activities of Apium leptophyllum are shown in Table 4.

Pharmacological Properties of Apium leptophyllum
The fruit has long been used as an anti-nephritic and anti-rheumatic as well as for the treatment of anorexia, tumors, vomiting and Mitch. [24]he presence of coumarins, phenolics, alkaloids, and a major source of flavonoids has been proven in previous research to have antibacterial, antioxidant, chemo preventive, and anti-mutagenic activity in the Volatile oil of the fruit and leaves. [10,11,24]Moreover, some Indian traditional practitioners have found the fruits to be beneficial in the treatment of bronchitis, cough, and asthma.In asthmatic patients, fruits have thermogenic and antispasmodic properties. [35]Apium leptophyllum is used to cure stomachaches and diarrhoea because of its powerful antibacterial, antifungal and anti-inflammatory qualities. [36]ti-microbial Properties Abd and co-workers in 1992 have reported that the oil of Apium leptophyllum had shown strong activity against both Gramnegative bacteria and Gram-positive.Apium leptophyllum was found significantly active against E. coli, S. dysenteriae, P. aeruginosa and V. cholerae strains tested.S, aureus and Pharmacognosy Reviews, Vol 17, Issue 33, Jan-Jun, 2023 The antimicrobial properties of Apium leptophyllum are shown in Table 5.

Anti-fungal Properties
Asamenew and other co-workers in 2008 have reported the antifungal activity of the oil of Apium leptophyllum and found that maximum fungal inhibitory potential against A. niger was 83.3 percent, somewhat greater than that observed against P. notatum (77.3 percent). [10]According to several studies, Apium leptophyllum harvested in Egypt had strong antifungal activity against Candida albicans and moderate activity against Cocciand rods, Gram-negative bacteria and Gram-positive bacteria and. [39,37]According to Salehi and other coworkers, the presence of Dillapiol and Myristicin in essential oils may have a synergistic impact, which could explain the greater antifungal activity against Asperigillus fumigatus and Aspergillus flavus.The methanolic extract of Apium leptophyllum also showed the strongest antifungal activity against Candida parapsilosis, Candida kreussei and Candida albicans. [40]The anti-fungal properties of Apium leptophyllum are shown in Table 6.

Anti-inflammatory and Anti-diabetic Properties
Various researchers have demonstrated anti-inflammatory activity of Apium leptophyllum.The Apium leptophyllum also shows anti-inflammatory properties.They have reported that the essential oil showed a stronger anti-inflammatory activity (49.54%) comparable to Indomethacin (42.29%), while those of 8-hydroxy cuminic acid and β-sitosterol were weaker. [22]The anti-inflammatory activity of the essential was also performed by using carrageenan-induced rat paw oedema model. [41]Salehi and other researchers in 2019 have reported that the ethanolic extracts of the seeds showed an anti-inflammatory effect against chronic inflammation induced by cotton pellet granuloma.The evidence presented above backs up the common use of these plants to treat pain and inflammation.Compounds derived from Apium leptophyllum have been examined for their anti-inflammatory properties in more recent research.Lutein, a naturally occurring flavone with a variety of biological activities, was found to have important anti-inflammatory activity in both acute and chronic inflammatory conditions. [18]Salehi and other researchers in 2019 Shigella spp.demonstrated moderate action against the oil. [37,10]The oil's anti-bacterial activity, especially against S. aureus is responsible for a variety of human clinical disorders marked by inflammation, tissue necrosis and abscess development. [38]he bacterial infection induced by S. aureus is most likely to blame for "Mitch" inflammation; therefore the use of fresh leaves of Apium leptophylum is used in the Ethiopian medicinal system for the curative agent of "Mitch". [10]Salehi and other researchers in 2019 determined the antimicrobial activity of the essential oil of Apium leptophyllum against Helicobacter pylori.Moderate antimicrobial activity was found against Salmonella typhi that are resistant to various antibiotics.They also demonstrated that the ethanolic fraction of Apium leptophyllum were significant effective against A. flavus.Due to presence of, selinene, free hydroxyls, limonene and other constituents that can combine with the carbohydrates and proteins in the bacterial cell wall, as well as the lipophilic character of these compounds, led to enzyme inhibition or accumulation in membranes, resulting in energy depletion, which is linked to their antibacterial properties. [66] Quercetin HCT, MCF [67]   Corosolic acid MCF, APC [68], [69]  leptophyllum and the cancer against they are used are shown in Table 7.

Authors' Contribution
M.S.R: Conceptualization, supervision, project administration, resources, funding acquisition, writing-review and editing, T.A.S: Conceptualization, methodology, writing-original draft preparation, S.Y.G: Writing-original draft preparation; All have also reported anti-diabetic activity of Apium leptophyllum and showed that hexane extract of the seeds of Apium leptophyllum effectively reduced glucose, triglyceride levels and cholesterol in streptozotocin (STZ)-induced diabetic rats; it also increased HDL and serum insulin as compared to the negative diabetic rats. [18]Apium leptophyllum was found to be toxicity free and safe as no alterations were found in Hematological, biochemical and histopathological studies. [42]ti-diarrhoeal and Anti-asthamatic Properties Apium leptophyllum have been reported to have anti-diarrheal and anti-asthmatic properties.The study for Anti-diarrheal properties of Apium leptophyllum was carried by Sahoo and other researchers in 2016.It was discovered that the flavonoid fraction of Apium leptophyllum fruit (FFALF) has anti-diarrheal qualities mediated by prevention of hyper secretion and gastrointestinal motility, confirming the plant's traditional use.[43] The antiasthmatic properties of Apium leptophyllum were carried by Sahoo and other researchers to confirm the traditional assertion that the flavonoid fraction of Apium leptophyllum fruit (FFALF) has antiasthmatic properties.Furthermore, in all of the animals, FFALF showed dose-dependent anti-asthmatic action.As a result, the FFALF was shown to have anti-asthmatic characteristics, most likely as a result of its membrane stabilizing properties, as well as lowering antibody formation and blocking antigen generated by histamine and acetylcholine.[35]

Anti-cancer Properties
Various studies have shown Anticancer potential of Apium leptophyllum.Helal and other coworkers in 2017 have evaluated anti-proliferative role of essential oil as well as1-nonadecanol, β-sitosterol, and 8-hydroxy cuminic acid on colorectal carcinoma (HCT-116), human hepatocellular carcinoma (HePG-2), human prostate carcinoma (PC-3) and mammary gland carcinoma (MCF-7) cell lines and found that, the essential oil and 8-hydroxy cuminic acid revealed the highest anti-proliferative activity against these cell lines. [23]Another study was carried out by Sahoo and other researchers in 2014 to demonstrate the chemopreventive potential of flavonoidal fractions of Apium leptophyllum fruits (FFALF) on Swiss mice.He reported that co-administration of FFALF reported significant activity against induced skin papilloma. [12]Another study was carried out by Ganesh and other researchers in 2019 to find in-vitro anti-proliferative potential of Apium leptophyllum against EAC Cell Lines.They used both aqueous and ethanolic extract to carry out anti-proliferative effect of Apium leptophyllum.The results revealed that ethanolic extract of Apium leptophyllum (EEAL) was more anti-cancerous against Ehrlich Ascites Carcinoma and was dose dependent.The Ethanolic extract showed 98.87% and Aqueous extract showed 87.32% and of cytotoxicity. [44]Phytochemicals present in Apium

Table 7 : Phytochemicals present in Apium leptophyllum and the type of cancer against which they are used.
Apium leptophyllum is an herbaceous plant and grows in various parts of the world.Different parts of the plants are rich in terms of vitamins, alkaloids, phenolics minerals and flavonoids which are responsible for its medicinal applications.Proven pharmacological activities (such as antioxidant activity, anti-inflammatory activity, antimicrobial activity, antiasthametic, antidiarroheal, antidiabetic and anticancer) of Apium leptophyllum would make it suitable to treat several diseases.Moreover, further extensive research investigations are needed to know the mechanism of action of Apium leptophyllum in treatment of various diseases and disorders thus can be utilized for the development of effective drug formulations for the well-being of humans.