Ethnotherapeutic Uses and Phytochemical Composition of Physalis peruviana L.: An Overview

Background Plant-derived medicines are widespread and continue to increase in traditional and modern medicine, especially in developing countries. Physalis peruviana L. is among the most used plants in conventional medication worldwide. This review aimed to highlight the ethnotherapeutic uses and phytochemical status of identified compounds in P. peruviana. Methods Data were collected from Google Scholar, PubMed/Medline, SciFinder, Science Direct, Scopus, the Wiley Online Library, Web of Science, and any other helpful search engine using Physalis peruviana as the primary keyword. Results Some countries, worldwide, use P. peruviana in their traditional medicine system to manage diverse ailments, mainly diseases and gastrointestinal tract disorders (25.33%). Leaf was the mostly used part (49.28%), prepared by decoction (31.58%) and overall administrated orally (53.57%) as the main route of admission. Around 502 phytoconstituents were identified in different plant parts, especially fruit (38.19%) ethanol/ethyl acetate extract. In most cases (36.17%), the solvent of the extract was not specified. Several phytochemical classes were found in the plant, especially terpenes (26.09%) and phenolic compounds (14.94%). Esters were also abundant (11.55%). In the terpenes category, carotenoids were the most abundant (11.15% followed by monoterpenes (8.76%) and diterpenes (3.18%). However, flavonoids (5.17%) followed by cinnamic acid derivatives (3.99%), monophenolic compounds (1.79%), and phenolic acids (1.33 M) are the most reported phenolic compounds. Hexadecanoic acid (palmitic acid) was the most cited (five times). Conclusion P. peruviana plays an essential role in managing diseases in some countries and is rich in chemical compounds, which need to be isolated and investigated pharmacologically before clinical trials.


Introduction
According to the World Health Organization (WHO), about 80% of the population in developing countries uses herbal medicine to meet their primary healthcare requirements [1]. Humans have used natural products since prehistoric times, which include animals, marine organisms, microorganisms, and plants, in medicines to prevent, diagnose, and treat diseases [2]. Plants still contribute primarily to health care, so many specific herbal extracts have been demonstrated to be productive for particular conditions [3]. More than 50,000 plants would possess therapeutic virtues globally. In Africa and Asia, it is estimated that more than 80 percent of the population uses traditional medicine for primary health care. is form of therapy remains prevalent in all world regions, and its use is rapidly spreading in developed countries [4]. priority plant for commercialization (used popularly for its berries and associated derivative products such as juice, jam, and wine). It is also used as food and has medicinal applications [63].
Local names, parts used, traditional utilization, preparation, and administration modes were documented. Figure 1 indicates that the leaves are the most used part (49.28%) followed by fruits (14.49%), whole plant (11.59%), roots (7.5%), stem (4.35%), aerial parts, and seeds (2.90%). However, bulbs, flowers, ripe fruits, and twigs were cited once (1.45%). In some cases, the used parts were not specified (1.45%). Leaves are the most used in the formulation of remedies, as indicated above. e frequent use of leaves is associated with ease of accessibility among the aboveground parts of plants in natural ecosystems [50].
Decoction has often been found as the effective formulation of herbal remedies as it is easy to prepare by mixing a drug with boiling water [64]. In this study (Figure 2), the decoction was used in almost 31.58% of all cases. However, other preparation modes have been found including juice (14.04%), maceration (8.77%), infusion (7.02%), extraction, and raw material (3.51%). In 19.30% of cases, the preparation mode was not reported.
P. peruviana is indicated to treat various diseases, mainly in humans. Rarely, it is used in the management of diseases in veterinary medicine. For example, in western Kenya, it is used for livestock tick prevention and control. e results in Figure 3 show that diseases and disorders of the gastrointestinal tract were the most treated by the plant (25.33%), followed by female genital tract and breast (13.33%), skin (9.33%), liver and biliary tract (8.01%), eye and ear (8.01%), immune system (5.33%), endocrine system (5.33%), respiratory system (2.67%), and metabolic disorders (2.67%). Diseases of bones, joints, skeletal muscle, and body fluid-related diseases and disorders represent 1.33%. Another category of diseases, including helminthiasis, inflammations, malaria, snake bite, fungal infections, bacterial infections, and smallpox, represents 17.33%. About 4000 species had ethnomedical data supporting the use of these plants to treat, and most of them were native to tropical countries due to the extraordinary biodiversity in these countries [65].
Mostly, oral route is the way of drug administration based on different formulations. Because of safety, good patient compliance, ease of ingestion, pain avoidance, and versatility to accommodate various types of drugs, the oral administration route is preferred over the different other administration routes of drug delivery [66]. Nevertheless, the route of the administration is not specified in a few cases (20.41%). Secondarily, bathe, tropical application, scratches, and steam inhalation are reported ( Figure 4).
ere are some specific indications in formulations or modes of drug administration. For example, in India, the plant is associated with Impatiens roylei and Stephania hernandifolia to treat jaundice. In the same way, in Uganda, the plant is combined with Solanum esculentum and Solanum melongena to manage skin problems in babies and 2 e Scientific World Journal  [42] e Scientific World Journal 3 honey in treating malaria. It is possible that combining several plants can produce a more pronounced pharmacological response than using a single plant due to the synergy of action between different constituents. According to Sofowora et al. [67], the combined effects were much more effective than individual ones. Rarely, duration of treatment and posology were mentioned. However, those two factors depended on the type of diseases treated and the parts used. For example, in Uganda, treating malaria needs seven days by taking two teaspoons three times a day of a decoction or half a glass thrice a day. In Tanzania, an application of leaf juice on the affected area twice a day was indicated to treat skin fungal infections or heating/topical application on to cuts and scratches in New Guinea for boils and ulcers. In Nepal, the treatment of jaundice in children could take from four to ten days. e voucher number of plant material was not specified in 63.46% against 36.54%. Overall, in research studies that involved plant or animal materials, providing voucher specimens is necessary for several reasons. e main reason is to keep a permanent record documenting the plant used in a specific study to trace the true identity and source of the plant material [68]. In most cases, the plant species look alike (morphologically and chemically), and it is quite possible to have a confusing error when harvesting. To be reassured of the real identity of the plant, it is crucial to have it authenticated with an expert, for example, a botanist. In the event of a future contestation, the voucher number recorded in the herbarium will always be essential to confirm the integrity of its identity. It is also vital for reproducibility, which is very critical in research.   Different parts of P. peruviana contain terpenes, and polyphenols represent the main two classes of identified phytoconstituents. ey represent 26.09% and 14.94%, respectively. In the terpenes category, carotenoids are the most representative (11.15%), followed by monoterpenes (8.76%), sesquiterpenes (5.57%), and diterpenes (3.18%). A considerable amount of sesquiterpenes (22.3%) and fatty acids (22.8%) has been found in P. angulata, a Physalis species close to P. peruviana, as volatile components of leaf essential oil [91]. However, phytol (17.88%) was the most diterpenes found in ethanolic extracts of leaves, roots, and fruits of P. minima, beyond other phytoconstituents, including fatty acids [92]. According to our results, phytol was identified right now, only in calyces and leaves of P. peruviana. e presence of phytoene can justify the richness of the plant in carotenoids. erefore, phytoene is an alkene hydrocarbon with 40 carbon atoms intermediate in the biosynthesis of carotenoids. e synthesis of phytoene is necessary for that of carotenoids in plants. e biosynthetic pathway from phytoene to violaxanthin is common to the genus Physalis [70]. Furthermore, carotenoid pigments from different species of the Physalis genus are primarily used in the food industry as food dyes for fats and oils. eir seeds can contain up to 30% fatty oil [93]. e presence of carotenoids in the Physalis genus has been confirmed by Ramadan [94]. All-trans-β-carotene, 9-cis-β-carotene, and all-trans-α-cryptoxanthin were the primary carotenoids found in the fruits.
Referring to phenolic compounds, flavonoids are the most phytoconstituents found (5.17%) in the plant than cinnamic acid derivatives (3.98%), monophenolic compounds (1.79%), phenolic acids (1.39%), coumarins (0.79%), phenolic esters (0.79%), chalcones (0.39%), phenolic aldehydes (0.39%), and stilbenes (0.19%). Similarly, phenolic, flavonoid, and phenolic acid contents were identified and quantified in different parts of five members of the Physalis genus including P. angulate, P. patula, P. subulata, P. solanacea, and P. hederifolia. However, quercetin, kaempferol, and phenolic acids were identified as the major phenolic phytoconstituents in those five plant species, in different     [74] e Scientific World Journal 7   10 e Scientific World Journal  [77] e Scientific World Journal 11   [84] e Scientific World Journal 13  Hexane/acetone/ethanol [72] e Scientific World Journal 15  [95]. Overall, monophenolic and polyphenolic compounds are synthesized and then accumulated in all plant tissues, but their concentration can be varied from different parts. Among phenolic compounds, phenolic acids and flavonoids are the most studied, mainly pharmacological properties exploited for medical purposes [96]. Gupta et al. [97] noted the strong influence of phenolic compounds and the carotenoid content with bioactivity. e plant also contains fatty acids, which are the most cited in the literature. For example, hexadecanoic acid (palmitic acid) was the most cited, five times (0.82%), followed by decanoic acid, linoleic acid, and octadecanoic acid, which were mentioned four times (0.66%). Hexadecanoic acid (palmitic acid) is the most common saturated fatty acid in plants, animals, and microorganisms, and linoleic acid is central in plant lipids. It is essential for humans (animals) because it is derived mainly from dietary plant oils [98].
Beyond the sucrose esters identified in plants (2.58%), others such as peruvioses A, B, C, D, and F had already been isolated before in the dichloromethane extract of the sticky exudate that covers the fruit [99,100]. Nicandroses, other sucrose esters, have been isolated in the Physalis genus. eir presence is confirmed in different species including P. nicandroides var. attenuata, P. solanaceus, P. sordida, and P. viscosa [5].
Steroids such as ergosterol, campesterol, stigmasterol, lanosterol, ß-sitosterol, Δ5-avenasterol, and Δ7-avenasterol have been reported in P. peruviana pomace and fruit juice. A number of the vitamins have been identified primarily in pomace and fruits, including 1,25-dihydroxy vitamin D2 (derived from vitamin D), vitamin B9 (folic  [88] e Scientific World Journal acid), vitamin K, vitamin E (α,β,c,δ-tocopherols), and biotin. A study on the phytochemical composition of goldenberry pomace confirmed the presence of those vitamins. In addition to vitamins A, D, and K, niacin, riboflavin, thiamin, pyridoxine, vitamin B12, choline chloride, and p-aminobenzoic acid have been identified and quantified [105,106]. Among ten alkaloids identified in the plant, cuscohygrine was subsequently isolated from the roots [107], and physoperuvine has already been isolated from P. peruviana roots [108]. e other alkaloids have been explicitly isolated in the aerial and roots. ey are the only parts of plants where alkaloids were identified.

Conclusion
P. peruviana plays a significant role in managing various pathologies of different organ systems, but its ethnotherapeutic use is strongly limited to a few countries. e plant is very rich in compounds, considering the number of identified compounds. Regarding phytochemical profiling, effort must be directed towards isolating and characterizing more compounds, particularly those that can present a significant therapeutic interest via extensive pharmacological investigations.

Disclosure
is study is part of the Ph.D. training of FMK. e funding agent had no role in the study design, data collection, data analysis, and writing of the present manuscript.

Data Availability
All relevant data are presented in the manuscript. However, any required further information can be provided by the corresponding author upon request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.