Myrica esculenta Buch.-Ham. ex D. Don: A Natural Source for Health Promotion and Disease Prevention

Myrica esculenta (Myricaceae) is a popular medicinal plant most commonly found in the sub-tropical Himalayas. It is widely used in folk medicine to treat several ailments such as asthma, cough, chronic bronchitis, ulcers, inflammation, anemia, fever, diarrhea, and ear, nose, and throat disorders. Due to its multidimensional pharmacological and therapeutic effects, it is well recognized in the ayurvedic pharmacopeia. However, the recent upsurge in M. esculenta use and demand has led to illicit harvesting by the horticultural trade and habitat loss, pushing the plant to the brink of extinction. Thus, the present review aims to provide updated information on M. esculenta botany, ethnomedicinal uses, phytochemistry, pharmacological effects, toxicity, and conservation methods, as well as also highlight prospective for future research. Particular emphasis is also given to its antioxidant potential in health promotion. In-depth literature was probed by searching several sources via online databases, texts, websites, and thesis. About 57 compounds were isolated and identified from M. esculenta, and the available reports on physicochemical parameters, nutritional and high-performance thin-layer chromatography analysis of bioactive plant parts are portrayed in a comparative manner. Friendly holistic conservation approaches offered by plant biotechnology applications, such as micropropagation, germplasm preservation, synthetic seed production, and hairy root technologies are also discussed. Nonetheless, further studies are needed to propose the mechanistic role of crude extracts and other bioactives, and even to explore the structure–function relationship of active components.


Introduction
Genus Myrica is a large group comprising more than 97 species in the Myricaceae family. This family contains woody plants native to the subtropical and temperate zones of the earth [1]. Plant species of this genus are distributed in China, Taiwan, Japan, Western Highland of Cameroon, North America, South Africa, Australia, Brazil, Ethiopia, Nepal, and India [2][3][4][5]. Specifically, Myrica esculenta Buch.-Ham. ex. D. Don named 'Hairy Bayberry' and widely known as Kaiphal or Kataphala in the Indian subcontinent, is broadly used in Ayurveda (traditional Indian system of medicine) [6][7][8]. But this plant also has other synonyms, such as Myrica sapida Wall. and Myrica farqhariana Wall. [5,9,10]. Myrica plants grow well in nitrogen-depleted soils, mixed forests, agricultural and marginal lands [1,11].  [19,20] "Katphaladi Churna" Treatment of fever, throat infection, respiratory disorders, and abdominal pain VHCA Ayurveda [19,20] "Pushyanuga Churna" Treatment for bleeding disorders and candidiasis AVN Ayurveda,Baidyanat-h [19,20] "Katphala Taila" Treatment of joint pain VHCA Ayurveda [19,20] "Arimedadi Taila" Helps to relieve tooth decay and breath problem IMIS Pharmaceuticals [19,20] "Mahavisagarbha Taila" Used for vata imbalance, neuromuscular conditions VHCA Ayurveda [19,20] "Bala Taila" Treatment of vata disorders, respiratory infections and weakness Patanjali [19,20] "Khadiradi Gutika" Treatment of dental, oral, throat and tonsillar infections Zandu [19,20] "Maha Vatagajankusa Rasa" Rheumatoid arthritis, Migraine, Paralysis, Cough, Cold, Asthma Dabur, Baidyanath, Shree Dhootapapeshwar [19,20] "Brihat Phala Ghrta" Treatment of infertility SN Pandit Ayurvedic [19,20] More recently, its numerous ethnomedicinal uses led researchers to explore M. esculenta phytochemistry further. For instance, tannins extracted from its bark are used as a dyeing agent [6]. Indeed, the presence of distinct bioactive compounds, such as alkaloids, flavonoids, glycosides, tannins, terpenoids, saponins, and volatile oils [8,21], has been increasingly reported as related to its pharmacological effects. For example, crude extracts and isolated compounds from M. esculenta exhibit both in vivo and in vitro pharmacological activities. Local tribes use the tree for timber, fuel, fodder, wood, likewise as used for tanning and getting yellow colored dye [22][23][24][25]. In spite of being a useful tree, the cultivation of the plant is incredibly restricted, and most of the traditional and commercial uses of M. esculenta rely solely on collections from the wild sources by endemic people [26]. Thus, wild sources of the species are underneath impending danger of extinction due to the increase in urbanization, overharvesting, negligence of sustainable use, and over-exploitation of forests and wastelands for industrial uses [27]. Due to the over-exploitation of the natural habitat, limited geographical prevalence and the unresolved problems inherent in seed vitality and germination, alternative propagation and conservation approaches are desperately needed to avoid the possible extinction of this vital species [8]. This species is fundamentally the same as M. rubra, which is ordinarily found in China and germination, alternative propagation and conservation approaches are desperately needed to avoid the possible extinction of this vital species [8]. This species is fundamentally the same as M. rubra, which is ordinarily found in China and Japan. However, M. esculenta contains fruits smaller than about 4-5 mm compared to the M. rubra fruits (12-15 mm) [28]. Although information on phenolic content and antioxidant activity of the fruit extract, juice, jam and marc of M. rubra [19,20,[29][30][31][32] is available, this information is lacking for M. esculenta. Previous reviews have suggested that myricetin is obtained mainly by members of the Myricaceae family [33,34] and is a key ingredient in many foods, besides to be used as a food additive due to its antioxidant activity and ability to protect lipids from oxidative damage [35]. It is one of the key ingredients of various foods and beverages. The compound has a wide range of potentialities that include strong antioxidant, anticancer, antidiabetic and anti-inflammatory effects, and can protect a wide variety of cells from in-vitro and in vivo lesions [36]. It was first isolated in the late eighteenth century from the bark of Myrica nagi Thunb. (Myricaceae), harvested in India, as light-yellow crystals [37].
In this sense, this review investigates the relevant information on botanical description, ethnomedicinal uses, phytochemistry, antioxidant activity, pharmacological activity and toxicity, along with conservation of M. esculenta. Its critical aspects as a natural source of antioxidant compounds for health promotion and disease prevention are also raised.

Research Methodology
The research methodology adopted for the selection of articles for this review is stipulated as flow chart in Figure 1.

Morphologicaland Microscopical Characteristics
Morphological characterization of M. esculenta plant and its parts (Figure 3a-d) describes that it is a small moderate sized evergreen woody tree with a height of 3-15 m. Its leaves are lanceolate, obovate, with diameter 9 × 3 cm, and lower surface shows light green; upper surface dark green in appearance [39,41].

Morphologicaland Microscopical Characteristics
Morphological characterization of M. esculenta plant and its parts (Figure 3a-d) describes that it is a small moderate sized evergreen woody tree with a height of 3-15 m. Its leaves are lanceolate, obovate, with diameter 9 × 3 cm, and lower surface shows light green; upper surface dark green in appearance [39,41].

Morphologicaland Microscopical Characteristics
Morphological characterization of M. esculenta plant and its parts (Figure 3a-d) describes that it is a small moderate sized evergreen woody tree with a height of 3-15 m. Its leaves are lanceolate, obovate, with diameter 9 × 3 cm, and lower surface shows light green; upper surface dark green in appearance [39,41].

Ethnomedicinal Uses
M. esculenta, a conventional ayurvedic plant, is used by different native population groups in multiple ways because of the various therapeutic uses of its bark, roots, fruits, leaves and flowers (Table 2) [20,49,55,56].

Ethnomedicinal Uses
M. esculenta, a conventional ayurvedic plant, is used by different native population groups in multiple ways because of the various therapeutic uses of its bark, roots, fruits, leaves and flowers (Table 2) [20,49,55,56].  Apart from these ethnomedicinal uses, various fruit industries in Himalaya used its fruits for making syrup, jam, and squash [70]. The Khasi tribe of Meghalaya uses its bark as fish poison while the extracted tannin from its bark is use as a tanning and dyeing agent [71]. Local peoples in Arunachal Pradesh use this tree for timber and fuel [22].

Pharmacological Profile
Extracts from M. esculenta possess a broad spectrum of pharmacological activities. Previous research revealed that phenolic compounds are highly active antioxidants, and such antioxidant-rich botanicals offer promising potential in the management of degenerative ailments. Phenolic compounds are secondary metabolites synthesized in plants in response to environmental stresses such as attacks from pathogens and insects, UV radiation, and injuries [5][6][7]. These phytochemicals have the ability to eliminate hydroxyl radicals [89], superoxide anion radicals [90], lipid peroxyl radicals [91] and even to chelate metals, besides to play a vital role in the stability of food products, as well as in the defense mechanisms of biological systems [4,8]. These molecules also prevent oxidative losses and have cytoprotective, anti-inflammatory, and adaptogenic properties. It was found that relatively high amounts of phenolic compounds are present in M. esculenta fruits than M. rubra [76]. The antioxidant activity of M. esculenta fruits and bark has been reported by using different antioxidant assays.

Conservation
Demolition of plant assets is an ordinary event. The current rate of eradication caused by mankind is about hundreds of time faster compared to the natural rate of elimination [117]. Due to training exercises in the Himalayan district, the existence of numerous therapeutically effective botanicals, including M. esculenta, are threatened with extinction. M. esculenta is exchanged and used most often as a conventional medication. Because of its numerous uses, application is on the rise through national and worldwide exchange, leading to the expansion of wild populaces. This has brought exceptional declines in population [118,119]. Due to its extreme overuse from regular natural surroundings, limited geographic predominance, and uncertain inalienable issues of seed practicality and seed germination, elective methodologies for spread and protection are urgently expected to evade the potential termination of this indispensable species [8,27]. The village forest council framework is a town-level establishment, and it has impressive potential for involving local communities in forest management for conservation [119]. Biotechnology offers new methods for enhancing biodiversity and biotechnological methodologies. For example, micropropagation systems have gotten more consideration and may assume a fundamental part in the foundation of hereditarily unvarying botanicals for the business. Hopefully, the advancement of coherent micropropagation conventions could ensure satisfactory availability of the M. esculenta plant (without forced ecological imperatives) with a consequent lessening in uncontrolled collecting weight on wild populaces [27]. Likewise, there are several highly valued traditional Indian ethnomedicinal plants having rich therapeutic potential and need immense scientific exploration and conservation strategies [120][121][122].

Conclusions and Future Perspectives
M. esculenta has been used for its restorative and dietary potentials, from the old-fashioned Ayurveda and Unani arrangement of solution. It is clear in this review that M. esculenta contains various phytochemicals, which are responsible for the therapeutic estimate of this plant. M. esculenta, and have been responsible for several pharmacological impacts in the treatment of different diseases, including asthma, diabetes, tumors, ulcer, tension; however, being a rich wellspring of vitamin C and polyphenolic compounds, there is a need to investigate the capacity of this plant for immunomodulatory, cardioprotective, nephroprotective, and neuroprotective movement. Although there are many analyses of chemical constituents, and the pharmacological activity has been reported for this plant, the mechanism of pharmacological action and the metabolites responsible for these activities should be studied in more detail. The population of this restorative and practical plant species is on the reverse because of excessive exploitation of woodlands and wastelands, neglect of practicable assets, poor development, and poor recovery of species in characteristic natural surroundings. Subsequently, a great opportunity has already passed to make the vital movement to expand its populace measure, efficiency, protection, and even use.

Abbreviations
The following abbreviations are used in this manuscript: