Medicinal plants have achieved broader recognition in recent times since these plants are natural products, they have minimal side effects and better effectiveness than their synthetic equivalents (Batiha et al., 2020). Approximately 80% of people in the world rely upon conventional medicine as a vital source of their basic medical care (Ekor, 2014). Most treatments use medicinal plant extracts and bioactive molecules (Michel et al., 2020). Medicinal plants are important sources of crude drugs that are used to treat various pathological conditions to maintain a status of well-being (Shakya, 2016). Medicinal plants have always been a potential source to treat various ailments, either in the form of traditional preparations or as pure active principles, and perhaps they are often the only source of medicine for the majority of folks in the developing nations (Taylor et al., 2001).

India has a long history of conventional medicinal systems and a lot of knowledge can be acquired from even a common man about herbal medicines of preventive and therapeutic significance. Out of 17,000–18,000 angiospermic species in India, over 7,000 plant species have been identified with medicinal properties (Kala et al., 2006) and of these, ∼1,748 plant species are being used as medicinal plants in the Himalayan region (Joshi et al., 2016). Medicinal plants have been reported to possess several biological activities such as anticancer (Mlilo and Sibanda, 2022), antimicrobial (Chan et al., 2022), anti-diabetic (Ahmed et al., 2022), anti-inflammatory (Rahmawati et al., 2021; Doe et al., 2022), antiviral (Shahrajabian et al., 2022), anti-feedant (Kerebba et al., 2022), antioxidant (Appiah-Opong et al., 2022), and anti-spasmolytic activities (Batiha et al., 2020; Hussain et al., 2020). These activities have been ascribed to their active principles viz: coumarins, glycosides, saponins, flavonoids, steroids, tannins, carotenoids, phenolics, phenols, alkaloids, terpenes, etc. (Nazir et al., 2020; Sarkar, 2020). One of the basic requirements for primary health care success is the accessibility and use of appropriate drugs. Conventional medicine is still the most inexpensive and easily available source of treatment in the primary healthcare system.

S. anquetilia is a medicinal plant that belongs to the genus Skimmia of the Rutaceae family (Saqib and Sultan, 2005). The plant is endemic to the Western Himalaya and is distributed in the mountain ranges of Afghanistan and Indian sub-continent: India, Pakistan, and Nepal (Nissar et al., 2018). In India, the plant originates in the subalpine region of the Garhwal (Gaur, 1999), Jammu and Kashmir, Uttar Pradesh, and Himachal Pradesh (Walters et al., 1986; Sharma et al., 1993). In the conventional medicinal system, different parts of the plant have been used for the treatment of various ailments in parts of the Western Himalayas of India, Nepal, and Pakistan (Epifano et al., 2015). The purpose of this review is to provide an up-to-date and comprehensive overview of the botany, phytochemistry, traditional uses, and pharmacological activities of S. anquetilia. Furthermore, the present knowledge obtained mainly from experimental studies was critically evaluated to provide evidence and validation for local and traditional uses of S. anquetilia and to suggest future research scenarios and prospective therapeutic uses for this plant.

The whole plant of S. anquetilia N.P. Taylor and Airy Shaw was obtained from the Doodhpathri area (geographical coordinates 74^o33′35.81″N and 33^o52′10.87″E) of Budgam district, Kashmir, India at an altitude of 2,814 m above msl. The voucher specimen No. 3152-(KASH) was identified and deposited at the Herbarium, Department of Botany, University of Kashmir. The plant specimen collection did not include endangered or protected species.

S. anquetilia is known as “Nair” in Garhwal and “Patrang,” “Nar,” “Barru” or “Shalangli” in Punjab, “Nairpatti,” “Nayalpatti” or “Nihar” in Kumaun, “Kasturchara” or “Gurlpatta” in Jaunsar, “Naer Patar,” “Inga,” “Patar,” “Nar,” or “Near” in Kashmir (Goel et al., 1989), and “Kedarpatti” in other hilly areas of India (Negi et al., 2011).

S. anquetilia is an aromatic, perennial, evergreen, gregarious, usually dioeciously, or monoclinous shrub (Gondwal et al., 2018), often cultivated for decorative purposes (Kumar et al., 2012; Figure 2). It has an erect, aerial, cylindrical, faintly fissured, densely branched, glabrous, yellowish, 1.5 m tall, and a 5′ wide stem. Leaves are alternate, simple, often crowded at the tips of branches, petiolate, unicostate, reticulate venation, coriaceous, marginate, oblanceolate, glands with essential oils, narrowly cuneate at base, acute at apex; terminal, paniculate, peduncle; with corymbose inflorescences. The root is tapering, thick, and branched. Flowers are yellowish, complete, indorous, hypogynous, pedicellate, and ebracteate; calyx (4 or 5), connate; petals (5), imbricate; stamens (5), filaments subulate, anthers ellipsoid, with fleshy drupaceous berry fruit, bright red-colored, ovoid (Nissar et al., 2016, 2021).

Ethnobotany is a field of research that applies indigenous plant knowledge to health care. In India S. anquetilia has long been used in Ayurveda and Unani system of medicine, which describes its numerous uses (Table 1). The paste prepared from the roots of S. anquetilia has been used as an antidote against scorpion and snake bites (Bhattarai, 1992; Ahmed et al., 2004; Qureshi et al., 2009; Gondwal et al., 2012b). The powder of the plant bark has been found effective in curing wounds and burns (Negi et al., 2011; Singh and Rawat, 2011). The cold infusion of fresh leaves has been used to treats smallpox (Namiki, 1990; Saqib and Sultan, 2005; Prakash et al., 2011; Kumar et al., 2012), headache, and fever (Bhattarai, 1992; Gaur et al., 1993). The smoke of dried leaves has been used for freshness (Bhattarai, 1992; Gaur et al., 1993; Kunwar et al., 2010), and air purification (Chopra et al., 1956; Chauhan et al., 2017). Some tribal sections of India use its leaves in the preparation of curries (Anon, 1966; Chauhan et al., 2017), an alcoholic drink “Soor” high in calories (Rana et al., 2004), and as a flavoring agent (Anon, 1966; Chauhan et al., 2017). A paste prepared with the mixture of leaves of S. anquetilia and turmeric has been used to treat inflammation and rheumatism (Negi et al., 2011; Singh and Rawat, 2011). In Nepal, leaf infusion is taken for headache and for freshness, leaves are aromatic and used for headache and general fever (Baral and Kurmi, 2006). Personal communications with locals highlighted that that the leaf extract is used to treat diabetes in the Kupwara district of Kashmir valley. Moreover, its dried leaf powder has been used as an insecticidal and pesticidal agent (Bhattarai, 1992). The whole plant has been used in anesthesia and to treat several other health complications like pneumonia, paralysis, and lung cancer (Wani et al., 2016).

The isolation and identification of secondary metabolites are vital to discover novel drugs to treat diseases. Several studies have been conducted on the phytoconstituents of S. anquetilia (Epifano et al., 2015). Over 130 compounds such as fatty acids and their esters, alkanes, alkenes, carboxylic acids, terpenes (such as monoterpenes, diterpenes, sesquiterpenes), phenylpropanoids, etc., have been identified using the GC-MS technique. Most of the phytochemicals have been identified from the essential oils of different parts of S. anquetilia. For instance, seventy compounds have been identified using the GC-MS technique from the essential oils of fruit pulp and seeds of S. anquetilia (Prakash et al., 2011). Common compounds found in both essential oils were fatty acids and their esters, whereas compounds such as α-cadinol, α-terpineol, selinene, neo-isolongifolene, linalool, cis-Z-α-bisabolene oxide, and aromadendrene were found to be the main difference among them (Prakash et al., 2011). Furthermore, more than fifty compounds have been identified from the essential oils of flowers and leaves of S. anquetilia and the majority of compounds were found to be monoterpenes and sesquiterpenes such as β-phellandrene (18.4, 1.8%), geijerene (15.0, 2.0%), germacrene B (2.0, 11.6%), linalyl acetate (11.2, 7.3%), linalool (9.4, 9.5%), α-terpineol (4.4, 5.6%), and pregeijerene (5.6, 0.2%) (Gondwal et al., 2012b). To date, only six glycosides (simple coumarins) namely, skimminan (Sharma et al., 2008a), ulopterol, skimmin, osthol, esculetin, and scopoletin (Sharma et al., 2008a,b) have been isolated through column chromatography and identified via nuclear magnetic resonance (NMR), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC), and nuclear overhauser effect spectroscopy (NOESY) techniques from the methanolic leaf extract of S. anquetilia. The identified phytoconstituents of S. anquetilia are presented in Table 2.

The varied traditional uses of S. anquetilia have contributed to the initiation of several pharmacological studies. Preceding research shows that the S. anquetilia extracts exhibit a wide array of bioactivities, viz: antibacterial (Sharma et al., 2008a), antioxidant, anti-inflammatory, and other activities like anti-feedant and anticancer activities (Gondwal et al., 2012a; Kumar et al., 2012; Negi et al., 2012; Wani et al., 2016; Table 3). At the same time, a wide array of in-vivo and in-vitro models has been used to evaluate the pharmacological properties of S. anquetilia. Evidence-based laboratory analysis indicates that petroleum ether, chloroform, ethyl-acetate, methanolic, and aqueous extracts of S. anquetilia possess several promising pharmacological properties.

S. anquetilia is proving to be an unreliable option for the future. Various active compounds viz, alkanes, alkenes, coumarins, carboxylic acids, fatty acids, and esters of fatty acids, terpenes (monoterpenes, diterpenes, sesquiterpenes), etc., have been reported to be the major bioactive compounds in this plant (Bhatt et al., 2021). The varied bioactivities including anti-arthritic (Verma et al., 2020), anticancer (Wani et al., 2016), anti-inflammatory, antibacterial (Nabi et al., 2022a,b), antioxidant, and anti-feedant (Gondwal et al., 2015) activities have been studied with potential findings. Despite the positive outcome, most of the studies are based on the in-vitro models and mechanisms of action are not well-studied. Various traditional medicinal sources indicate that this plant has been used to treat diabetes, smallpox, burn injuries, etc., but, no pharmacological studies have been conducted to validate these activities. Furthermore, in some areas, there is inadequate information and limited research is available. Therefore, further studies concerning the basic chemical composition of phytoconstituents and the mechanisms involved in traditional uses are needed. The pharmacological activities must be experimented to the next levels for generation of novel drugs. This might prove helpful to use its immense therapeutic efficacy as a potent phytomedicine. Thus, systemic research experiments must be carried out for the development of drugs and medicines for their better economic and therapeutic utilization.

S. anquetilia is probably a possible herbal treatment for various diseases. The plant provides several promising perspectives for both traditional as well as modern medicine. S. anquetilia is a wealthy source of essential oils containing various important bioactive compounds but there is inadequate information concerning the basic chemical composition and their mechanisms involved. Most of the plant parts have been used in traditional medicine including leaves, stem, flower, fruit, and root bark. Therefore, determining research analysis of the bioactive constituents is needed, particularly its pharmacological properties and toxicity in terms of both in-vitro as well as in-vivo test systems to authenticate the safety of such plant-based phytochemicals and to develop standard novel drugs.

MN: conceptualization and writing—review and editing the manuscript. NT and BAG: reviewing and editing the manuscript. All authors contributed to the article and approved the submitted version.