Phytochemistry of Uvaria narum : A Multifaceted Perspective and Ethnopharmacological Potential †

: The blooming ethnomedicinal plant Uvaria narum (Dunal) Wall is mostly found in the deep forests of the Western Ghats and belongs to the Annonaceae family. Uvaria narum is a spreading, pubescent shrub with large, dark bluish-green leaves. Phytochemistry and pharmacognostic studies have revealed that the plant possesses a variety of phytochemicals that are remarkable and beneﬁcial to humans. The plant also possesses a number of beneﬁcial properties, such as antioxidant activity exhibited by the presence of polyphenols and tannins, antifungal activity brought on by the benzoic acid moiety, and tumour-ﬁghting ability contributed by terpenoid and alkaloids. The presence of phytoconstituents in the plant has been attributed to the various medicinal properties of the plant, such as anticancer activity. The plant may also be considered for use against ageing and other diseases caused by free radicals. In vitro cytotoxicity is due to terpenoids, phytosterols, and ﬂavonoids, whereas the liver is protected by ﬂavonoids. The chemical proﬁle of the plant shows that acetogenins, including stereoisomers, are important constituents of the root bark. Eczema, itching, varicose veins, haemorrhoids, jaundice, inﬂammation, and fever are the main ailments for which this herb is used.


Introduction
India, which is aptly known as the Botanical Garden of the World, is the country that produces the most medicinal plants. Several medicinal herbs have been used by the indigenous system of medicine for thousands of years. India has a valuable heritage of herbal remedies for various ailments [1]. About 120 genera and more than 2000 species make up the enormous plant family known as Annonaceae. It is a highly uniform family in terms of habitat and anatomy. This family is valuable economically because it produces edible fruits and oils [2]. Approximately 210 species of the Annonaceae family have been identified, and they are widely distributed in tropical and subtropical wet forests in Africa, Madagascar, continental Asia, Malaysia, northern Australia, and Melanesia. Some Uvaria species are known to possess biologically valuable compounds, which have a number of therapeutic characteristics, and are often evergreen [3]. Uvaria is a genus of flowering plants in the soursop family Annonaceae. Because several species in this genus produce edible fruits that resemble grapes, the name Uvaria is derived from the Latin word uva, which means grape. These are spectacular bushes with sparsely haired branch lets. They have huge, woody stems and are climbing shrubs. Uvaria narum is a sizable straggling shrub with dark bluish-green leaves that is woody and stellately hairy [1]. This article seeks to give a thorough overview of Uvaria narum's botanical characteristics, phytochemistry, ethnopharmacology, and ethnomedical applications.

. Global Distribution
Uvaria narum is found in South India and Sri Lanka.

Indian Distribution
Uvaria narum is particularly found in southern India, mainly in the forests of Western Ghats from South Kanara to Travancore and the hills of Salem. It is occasionally distributed in the southern dry mixed deciduous forests at low altitudes.

Leaves
Leaves are simple alternate lanceolate; oblong to elliptic; about 10-16 cm × 2.5-6 cm across; apex acuminate; asymmetrical; dark green; base rounded, oblong pointed, or long pointed; hair lesson both sides; and stalks short and less than 6 mm. Crushed leaves smell like cinnamon.

Seeds
Seeds are around 4-6 in a row, compressed or ovoid, chestnut brown, and sub-orbicular, and have the extremities of the carpels that are plano-convex and middle ones that are compressed and nearly flat.

Flowering/Fruiting
The season of flowering is from November to December, and fruiting is from December to April.

Soil Requirement
Sandy loam soil with a loose structure and good drainage is needed [1,4].

Phytochemistry
Investigations into the phytochemistry of plants have identified various types of compounds with a variety of structural characteristics, and these compounds are still a rich source of novel natural products. Uvaria narum (Annonaceae) is one of the less chemically studied species in this intriguing group, according to a chemical literature review. Oils and fatty acids are discovered to be abundant in a number of Annonaceae species. Before 1982, fatty acids with an abnormally high molecular weight that were insecticidal were found in the seeds of Annonaceae species. These substances appear to have later been classified as lipids and fatty acids as a new class of natural goods known as tetrahydrofuranoid acetogenins. It has been discovered that certain Annonaceae plants, including Uvaria narum, contain polyphenolic chemicals. Many species of the Annonaceae family include phenolic acids, including caffeic acid, p-hydroxy benzoic acid, p-coumaric acid, and vanillic acid. The leaves of several members contain common flavonoids, including quercetin, quercitrin, and rutin.
Due to the presence of essential oils, many Annonaceae species are aromatic. Their oils typically contain monoterpenes, sesquiterpenes, or aromatic chemicals that are wellknown.There are species of Uvaria from specific Annonaceae genera that elaborate aromatic chemicals. In numerous Uvaria species, benzylbenzoate or its derivatives are frequently found. It seems that the potential to use benzyl or benzoyl groups to substitute various kinds of secondary metabolites is a recurring topic in the chemistry of Uvaria. Through research on various Uvaria species, a new class of secondary metabolites known as polyoxygenated cyclohexene derivatives combined with benzoyl esters has been discovered. They belong to a tiny family of secondary metabolites found in plants, and the curiosity about these peculiar substances has led to enquiries on their biogenesis [2].
The crude leaf aqueous extracts of Uvaria narum revealed the presence of alkaloid carbohydrate, coumarins, flavonoids, phenols, proteins, quinones, sterols, and terpenoides according to the preliminary phytochemical screening [5].Similar studies were conducted using a leaf extract that was dissolved in methanol and contained phenols, saponins, glycosides, and steroids. Carbohydrate, coumarins, phenols, phytosterols, proteins, sterols, and terpenoids were discovered in the chloroform extract. Glycosides, phenols, phytosterols, proteins, terpenoids, alkaloids, and carbohydrate were found in the acetone extract of Uvaria narum leaves. Steroids are recognised to be crucial for their cardiotonic effects in Uvaria narum, as well as having insecticidal and antibacterial characteristics [6][7][8][9]. The structures of some of the phytochemicals found in Uvaria narum are shown in Figure 1.

Ethnopharmacology
The various therapeutic activities proved by many researchers are mentioned next.

Ethnopharmacology
The various therapeutic activities proved by many researchers are mentioned next.

Antioxidant Activity
When compared to previous studies, the level of antioxidant activity of 523.70 µM (Fe)/gm root powder of U. narum's whole-root extract is promising. As antioxidant activity is directly proportional to the phenolic compounds in plants, this activity may be attributed to 0.8% of phenols present in the total root powder. Therefore, U. narum's whole-root extract could be used medicinally as a potential free-radical scavenger. The plant may also be used as a defence against ageing and other diseases brought on by free radicals [1,11].

Antibacterial Activity
The antibacterial activity of the sample was analysed usingstandard tube dilution procedures with some modifications. In terms of antibacterial activity, the plant showed inhibitory properties against both Gram-positive and Gram-negative bacteria, namely Staphylococcus aureus, Escherichia coli, Bacillus spp., and Lactobacillus ferment. Herbs frequently have antibacterial properties, especially when used as drugs to treat skin conditions. Therefore, given that the plant has been used as a medicine to treat skin conditions, it is not surprising that it possesses antibacterial action against a diverse variety of bacterial species. As a result, the plant may be used to treat skin conditions, such as eczema and others brought on by bacterial infections [11][12][13].

Hepatoprotective Activity
Significant hepatoprotective action is demonstrated by the ethanolic extract of U. narum leaves against CCl 4 -induced liver damage in rats. This might be because of the presence of identified phytoconstituents, particularly flavonoids with antioxidant properties. A number of plants are being used for the treatment of hepatic disorders, and Uvaria narum is one of the potential plants for liver diseases, such as jaundice. The hepatoprotective activity of its extract was found in carbon-tetrachloride-induced liver toxicity, paracetamol-induced liver toxicity, and thiocetamide-induced liver toxicity. The hepatoprotective potential of the leaves of Uvaria narum (Annonaceae) was found by noting elevation in hepatic biomarkers, such as SGPT, SGOT, ALP, bilirubin, and other biochemical parameters, such as cholesterol, triglycerides, urea, and tissue LPO, and a decrease in total protein, albumin, glucose, and tissue GSH, CAT, and SOD in CCl 4 -induced liver toxicity [14].

Antitumour Activity
Plants have strong immune-modulating and antioxidant characteristics that promote anticancer action. It was discovered that taxol and podophyllotoxin were effective in treating refractory ovarian, breast, and other malignancies. A good source of potential cytotoxic alkaloids and antraquinones is the seed oil of Uvaria narum. The phytoconstituents terpenoids and alkaloids found in Uvaria narum contribute to its antitumour action [1].

In Vitro Cytotoxicity
Using the trypan blue exclusion method, the cytotoxic effects of each extract on Ehrlich's ascites carcinoma (EAC), Dalton's lymphoma ascites (DLA), and normal rat spleen cells were assessed. Extracts of PE, CHL, acetone (ACT), and methanol (MeOH) demonstrated a strong toxic effect on these cells. The aqueous extract, however, proved nontoxic. Petroleum ether extract chemicals, which are toxic to cancer cell lines but less deadly to healthy spleen cells, serve as an example of differential cytotoxicity. In the phytochemical screening and TLC analysis of petroleum extract, terpenoid and phytosterol are determined to be two of the major phytoconstituents. The cytotoxic effect of the PE extract is therefore anticipated to be connected to its terpenoidal concentration. The cytotoxicity demonstrated by PE extract was selective, being more toxic to cancer cells than to normal spleen cells (IC50 for DLA was 19 ± 0.57 and that for EAC cells was 38 ± 0.74 g/mL, while over 100 g/mL for normal spleen cells). CHL, ACT, and MeOH extracts demonstrated the potential for cytotoxicity, and they have cytotoxic effects on cancer cells that are comparable to those of normal cells. This suggests that U. narum leaves are an important source of physiologically significant cytotoxic phytoconstituents [15].

Antidiabetic Activity
The earlier trend in diabetes treatment involved oral administration or injections, which necessitated careful examination of natural products, particularly Uvarianarum, by attempting to identify phytochemicals and chemical constituents as well as conducting clinical trials on natural products and their analogues in drug discovery studies. According to a review of many literary works, diabetes can be treated with plant leaves. Uvaria narum's methanolic extract substantially reduced the activity of glucosidase and amylase. Acarbose was used as a reference medication to quantify these inhibitory effects. Additionally, the cell showed no cytotoxic effects due to Uvaria narum. Amylase and glucosidase activities were effectively inhibited by the Uvaria narum extract in a good percentage. UN extract inhibited amylase activity by 71.31%, while the control medication acarbose inhibited it by 88.54%. In addition, the extract inhibited glucosidase activity by 79.11%, whereas acarbose inhibited it by 87.35%. Additionally, IC50 values were found. Furthermore, after being exposed to the extract, 75.49% of 3T3-L1 cells took up glucose and 70.67% of them expressed GLUT4 [16].

Antifungal Activity
In traditional and ethnomedical practices, Uvaria narum has been used to treat gastrointestinal issues, jaundice, fever, and skin ailments. The acetone extract of U. narum's leaves showed extremely good antifungal activity in preliminary antifungal testing. Using bioactivity-guided fractionation, the active ingredient in the acetone extract of U. narum leaves was identified. It was then characterised as a novel compound called 2-E-(2"-oxo-5"-acetoxy cyclopent-3"-en-1"-ylidene) ethyl benzoate using NMR, IR, and mass spectroscopic methods. Viable isolation has shown excellent effectiveness against the fungus Colletotrichum gloeosporioides [17]. Uvaria narum was tested against two important plant fungal pathogens, Fusarium moniliforme and Corynespora cassiicola. The leaves of Uvaria narum were subjected to sequential Soxhlet extraction in four solvents, i.e., petroleum ether (PE), chloroform (Chl), acetone (Ac), and methanol (Me). The extracts thus obtained were subjected to antifungal tests using the poison food technique. The sequentially extracted PE extract and the chloroform extract derived thereafter inhibited fungal growth by 65% and about 49%, respectively, in the case of Fusarium and 70% and 45%, respectively, in the case of Corynespora [18].

Antihelmintic Activity
Acetogenins were tested at concentrations of 0.05%, 0.15%, 0.25%, 0.75%, and 1.25%, and the crude extract was tested at concentrations of 0.1%, 0.3%, 0.5%, and 2.5%. The same ethanol/water mixtures (30% ethanol) in which drug solutions were prepared were used, and mebendazole was used as the standard drug. At every concentration, the extract exhibited a notable inhibitory effect, and when compared to the control, it exhibited almost 0.5% inhibition. This demonstrated the effectiveness of U. narum's antihelmintic activity [13].

Antiproliferative Activity
To measure antiproliferative activity, the MTT test was performed. Uvaria narum seed oil caused a dose-dependent reduction in cell viability in Vero (normal monkey kidney cells), HCT-15 (human colorectal adenocarcinoma cells), HepG2 (hepatocellular carcinoma cells), and HeLa cells (human cervical carcinoma cells) in culturesexposed to it at various concentrations, indicating that it has antiproliferative potential. The viability of all cells was shown to decrease depending on the amount of oil, and all cells were susceptible to UNSO.

Ethnomedicinal Applications
Uvaria narum is mostly used to treat patients with skin conditions, such as dermatitis andpityriasis, and constipation. It is also used to treat fever, jaundice, haemorrhoids, varicose veins, and irritation and itching. In rheumatic swelling, jaundice, biliousness, and fever, leaves are advised. The root is used to cure typhoid, jaundice, fever, and biliousness. Women are given a decoction of the root bark to manage fits during labour. It is also used for skin conditions, such as eczema; gastrointestinal issues in children; and rheumatism. The oil reduces liver burning when extracted from the root. Uvaria narumwhole-root extract may be used medicinally as a potential free-radical scavenger. The plant may also be used as a defence against ageing and other diseases brought on by free radicals. For gastrointestinal disorders, Uvaria's aerial portions are used [1,20].

Conclusions
This review of Uvaria narum shows that the plant is significant because of its therapeutic benefits and extensive phytochemical profile. The plant displays a good amount of phenols, tannins, and antioxidants. The chemical composition of the plant also reveals that stereoisomers and acetogenins are significant components of the root bark. Additionally discovered in isolation are glutinone, glutinol, beta-sitosterol, taraxerol, and benzyl benzoate. According to research that has been written about a variety of plants, the existence of these phytoconstituents in Uvaria narum has been linked to various medical qualities in the plants, such as anticancer, antioxidant, anthelmintic, antiproliferative, hepatoprotective, antitumour, and antibacterial activities. As a result, it is used to treat rheumatic infections, as well as eczema, biliousness, jaundice, and gastrointestinal issues.